Administration of low doses of TSH result in a rapid increase in the metabolic rate of young lambs

A low dose of TSH (Thyroid Stimulating Hormone) can induce a rapid increase in VO2 and the response is dose dependent. Lambs aged 36 to 289 h were used. 5.0 i.u./kg TSH, the highest dose used, caused an initial inhibition of response but during the second and third post injection hours VO2 increased to control level. The intermediate TSH dose, 1.0 i.u./kg TSH resulted in a clear increase in VO2 even in the first post-injection hour, which further increased in the second and third hours. This change was significantly greater than in controls. Animals treated with the lowest dose, 0.5 i.u./kg TSH divided themselves into 2 distinct populations: responders, where an immediate and significant increase in VO2 occurred and non responders, where a small inhibition of metabolism was evident. The responder group had a significantly lower pre-injection VO2 and a significantly lower mean body weight, than the non responders. In the responders, the stimulation of metabolism was greater than at either of the higher TSH doses. These results indicate that low, but not high doses of TSH induce a rapid metabolic response. The argument in favour of a short-term role for thyroid hormones is thus strengthened.     

Induction of hepatic mitochondrial alpha-glycerophosphate dehydrogenase by L-triiodothyronine in Singi fish (Heteropneustes fossilis Bloch)

A single injection of L-triiodothyronine (T3) in different doses (0.25, 0.5, 5, 20 and 50 micrograms/g) increased the hepatic mitochondrial cytochrome-linked alpha-glycerophosphate dehydrogenase (alpha-GPD) activity and mitochondrial protein content of Singi fish, as observed on the 3rd day. A non-linear dose-response relationship with respect to enzyme activity was observed with different doses of T3. A low dose of 0.1 micrograms of T3 per g failed to cause any change in alpha-GPD activity and mitochondrial protein content of the liver. The enhancement of alpha-GPD activity over the control level with a low and a high dose of T3, viz., 0.5 and 5 micrograms/g, was followed from the 1st to the 7th day, when it was found that enzyme activity reached the maximum level on the 3rd day and then gradually declined to the control value on the 7th day. The percentage increase in enzyme activity with 5 micrograms/g was higher than that with 0.5 microgram/g from the 2nd to 5th day. Compared to the control, these two doses of T3 caused an increase in alpha-GPD activity from the 1st to the 6th day. Cycloheximide inhibited the T3-induced increase in alpha-GPD activity, mitochondrial and total protein content of liver. Immersion of Singi fishes in thiourea-containing (1 mg/ml) medium for 30 days showed a fall in hepatic alpha-GPD activity in comparison to the euthyroid control. A single injection of T3 (0.5 microgram/g) to the hypothyroid fish recovered alpha-GPD activity to more than the euthyroid control level. An increase in mitochondrial protein content in the T3-injected hypothyroid fish has been observed. DNA content of the fish liver remained unchanged in every experimental condition. The results thus showed the significant responsiveness of the fish liver to thyroid hormone.     

Effects of TRH on circulating growth hormone, prolactin and triiodothyronine levels in the bovine.

The effects of administration of synthetic thyrotropin-releasing hormone (TRH) on circulating growth hormone (GH), PROLACTIN (PRL) and triiodothyronine (T3) levels of lactating dairy cows, non-lactating dairy heifers, and beef cows were studied. Intravenous administration of 0.1, 1, and 5 microgram of TRH per kg of body weight (bw) elevated plasma GH and PRL levels of lactating cows within 5 min. The plasma GH and PRL levels increased in proportion to the dose of TRH and reached a peak 10 to 30 min after TRH injection. Intravenous administration of 1 microgram of TRH per kg of bw to 7 non-lactating heifers, 14 lactating dairy cows, and 5 non-lactating beef cows elevated plasma GH level to peak values after 15 min, the increase rates being 6.9, 5.6, and 3.8 times as high as those in the pretreatment levels. The mean maximum vale was also in that order. Plasma T3 levels of non lactating dairy heifers at pre- and post-injection of TRH were significantly higher than those of lactating cows. The peak values of plasma PRL were obtained between 5 to 30 min after TRH administration. The increase rates of lactating dairy cows, heifers, and beef cows were 19.2, 13.9, and 20.9 times as high as those in the pretreatment. In contrast to GH and T3, plasma PRL levels of both pre- and post-injection with TRH in lactating cows and heifers were significantly higher in May than in October, though the increase rates were similar. Plasma PRL levels of lactating dairy cows at pre- and post-injection with TRH were significantly higher than those of non-lactating heifers. Subcutaneous administration of TRH was also effective to increase plasma TH, rl, and T3 levels in lactating cows. No significant change of GH or PRL response to TRH was observed after a short-term pretreatment of thyroid hormones.     

Nuclear activation by thyroid hormone in liver of Singi fish: changes in different ion-specific adenosine triphosphatases activities

Various ion-dependent (Na+K+, Ca++ and Mg++) ATPases activities in liver cell nuclear membrane have been determined after a single injection of different doses (0.01, 0.025, 0.05, 0.1, 0.25, 0.5, 1, 2 and 4 micrograms/g) of L-triiodothyronine (T3) in Singi fish, Heteropneustes fossilis Bloch. Administration of T3 at a minimum effective dose of 0.05 micrograms upto 4 micrograms/g induced a rise (14 to 43% over control value) in the Na+K+-ATPase activity in a dose-dependent fashion maximum upto 1 microgram/g dose, whereas Ca++-ATPase showed a dose-dependent increase (20 to 43% over control) with 0.25-1 microgram/g of T3, although the increase in the respective enzyme activity was maintained upto 4 micrograms/g of T3 dose. Mg++-ATPase activity in liver cell nuclear membrane was found to be increased at 1 microgram-4 micrograms/g of T3 dose, showing a similar magnitude of increase (7% over the control value) with these doses of T3. Other doses of T3 (0.01 and 0.025 micrograms/g) were ineffective in altering the different ion-specific ATPase activity. Treatment of Singi fish with thiourea (1 mg/ml) for 30 days caused a significant fall in Na+K+, Ca++ and Mg++-ATPase activities upto 21%, 17% and 5%, respectively, below the euthyroid control level. A single injection of T3 at the dose of 1 microgram/g in the hypothyroid fish raised the Na+K+ and Ca++-ATPase activities to about 36% over the control value, and the Mg++-ATPase activity was restored to only the control level. Thus a dose-dependent nuclear effect of T3 is evident from the present investigation.     

Demonstration of hepatic cytosolic malic enzyme activity as a thyroid hormone sensitive physiologic parameter in a teleost, Heteropneustes fossilis bloch

Single injections of various doses (0.1, 0.25, 0.5, 5 and 20 micrograms/g) of T3 significantly increased the cytosolic malic enzyme activity (delta OD/min/mg cytosolic protein) in liver of Singi fish Heteropneustes fossilis Bloch, in a dose-dependent nature, maximum up to 5 micrograms/g dose on the 3rd day in comparison to the control. There was no difference in the enzyme activity between 5 and 20 micrograms/g of T3 doses. When the enzyme activity was expressed per mg DNA, the dose-dependent increase in the malic enzyme activity was observed upto 0.5 microgram/g of T3, whereas a fall in the enzyme activity was noticed with 5 and 20 micrograms/g of T3 doses. Lowering the dose of T3 to 0.05 microgram/g was without any effect on the malic enzyme activity (delta OD/min/mg cytosolic protein or DNA). Hepatic cytosolic protein content showed a biphasic nature of variation, significant increase with single injections of 0.05, 0.1, 0.25 and 0.5 microgram/g and a fall with 5 and 20 micrograms/g of T3 doses in comparison to the untreated control. Cycloheximide treatments of the Singi fishes counteracted both the T3-induced rise in the hepatic cytosolic malic enzyme activity (delta OD/min/mg cytosolic protein or DNA) and the hepatic cytosolic protein contents. Thiourea-treated hypothyroid fishes showed significantly decreased level of malic enzyme activity (delta OD/min/mg cytosolic protein or DNA) and cytosolic protein content in liver. A single injection of T3 at 0.25 microgram/g to the thiourea-treated fishes not only recovered but also increased the enzyme activity and cytosolic protein content above the untreated control values.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of the pituitary-adrenal axis in the hyperthermia induced by acute peripheral or central (preoptic anterior hypothalamus) administration of morphine to unrestrained rats

The role of the pituitary-adrenal axis in the mediation of morphine-induced hyperthermia of conscious, unrestrained rats was investigated. Rectal (TR) and tail (Tt) temperatures and oxygen uptake rates (VO2) were measured following peripheral or central injection of morphine sulphate (MS) in groups of Sprague-Dawley rats before and after adrenalectomy (adx), hypophysectomy (hyp), or pituitary suppression (via dexamethasone treatment). The hyperthermic TR responses of groups given MS either subcutaneously (5 or 15 mg/kg) or directly into the preoptic anterior hypothalamus (POAH, 1 or 10 micrograms/microL) before adx were not different upon retesting with the same dose of MS 2 weeks later following adx. The hyperthermia with MS was not caused by vasoconstriction or by increases in basal metabolic rate, for Tt rose after the opiate injections whereas oxygen uptake rates (VO2) were reduced. Unexpectedly, the TR following POAH injections of sterile saline (SS) or deionized water after adx increased from those seen before adx. Adx groups supplemented with dexamethasone phosphate (either chronically with 20 micrograms/kg daily for 2 weeks post-adx before retesting with MS or acutely with 250 micrograms/kg 2 h before retesting) showed a hyperthermia to MS (5 mg/kg sc or 1.0 microgram/microL POAH) similar to that seen before adx. However, dexamethasone phosphate (250 micrograms/kg) supplementation to adx rats, that received POAH injections of SS, did reduce the rise in TR. Hyp rats given MS (5 mg/kg, sc) also evoked hyperthermic responses similar to those of non-hyp control groups. The results clearly show that the acute hyperthermia of unrestrained rats induced by either peripheral or central injections of morphine is not caused by activation of the pituitary-adrenal axis.     

Vasoactive properties of dihomo-gamma-linolenic acid and series one prostaglandins in a freshwater teleost, Channa maculata

1. Prostaglandins A1, B1, E1 and F1 alpha (2-120 micrograms/kg), arachidonic acid and dihomo-gamma-linolenic acid (0.1-2 mg/kg) were injected intravenously into Channa maculata and changes in arterial blood pressure were recorded. 2. Injection of PGF1 alpha had no significant effect on arterial blood pressure. Injection of PGA1 and PGE1 was followed by dose-dependent hypotension whereas injection of PGB1 elicited significant dose-dependent increase in arterial blood pressure. 3. Both dihomo-gamma-linolenic acid and arachidonic acid were also depressor agents but dihomo-gamma-linolenic acid was more potent. 4. A single bolus intravenous injection of indomethacin (5 mg/kg) or 4 daily intraperitoneal injections (4 x 10 mg/kg) significantly lowered arterial blood pressure. One hour after pre-treatment of indomethacin, the vascular effects of both prostaglandin precursors were abolished. 5. It appears that the vascular effects of prostaglandins in Channa maculata are qualitatively different from those reported for mammals.     

Analysis of food stimulation of gastrin release in dogs by a panel of inhibitors

The release of gastrin into the serum of five conscious gastric fistula dogs after a meat meal was monitored for 2 hours. Neither the rate of increase in serum gastrin nor the 2 hour cumulative integrated gastrin response was changed by administration of small doses of somatostatin tetradecapeptide (0.5 microgram/kg.hr IV for 2 hr), 16-16 dimethyl prostaglandin E2 (0.25 microgram/kg.hr IV for 2 hr or 1 microgram/kg intragastrically), or bethanechol (20 micrograms/kg.hr IV for 2 hr). Acidification of the food in the antrum to pH 1.2 to 1.4 eliminated serum gastrin release in response to food. In control studies, serum gastrin levels were not altered by IV administration of saline for 2 hr with no food or when a plate of food was held just out of the dogs' reach (teasing). Food-stimulated gastrin release was contrasted with that stimulated by bombesin under identical laboratory conditions [17]. In each case, antral acidification, somatostatin, prostaglandin E2 and bethanechol affected bombesin-stimulated gastrin release differently from that stimulated by food. We conclude that food and bombesin release gastrin by different pathways.     

Thyroid hormone-induced changes in different ion-specific adenosine triphosphatase activities in liver of Singi fish Heteropneustes fossilis (Bloch)

A single injection of different doses of T3 (0.5, 5, 20, and 50 micrograms/g) to Singi fish caused an increase in Na+K+-ATPase activity in crude liver homogenate in a dose-dependent non-linear fashion on the 3rd d. Ca++- and Mg++-ATPase activity increased only with 20 and 50 micrograms/g of T3. Lowering the dose of T3 to 0.1 microgram and 0.25 microgram/g in a single injection had not effect on these enzyme activities. TETRAC (1, 2, and 4 micrograms/g) and TRIAC (2 and 4 micrograms/g) in a single injection enhanced the activities of Na+K+-ATPase, but Ca++- and Mg++-ATPase activities remained unchanged on the 3rd d. Immersion of Singi fish in thiourea-containing medium (1 mg/ml) for 30 d caused reduction in Na+K+-ATPase activity, but Ca++- and Mg++-ATPase activity remained unaltered. The reduced level of Na+K+-ATPase activity in the thiourea-treated hypothyroid fish was recovered and even brought above the control level by a single injection of T3 at the dose of 0.5 microgram/g. Differential sensitivity of various ion-specific ATPases to T3 in liver of Singi fish is thus documented.     

Frequent occurrence of polyovular follicles in ovaries of mice exposed neonatally to diethylstilbestrol

The occurrence of polyovular follicles (PF) was examined at 10-34 days of age in the ovaries of BALB/cCrgl female mice given five daily injections of 0.1 microgram diethylstilbestrol (DES), 2 micrograms DES, 100 micrograms progesterone (P), 137 micrograms 17 alpha-hydroxyprogesterone caproate (HPC), 20 micrograms testosterone (T), 20 micrograms 5 alpha-dihydrotestosterone (5 alpha-DHT), or oil vehicle alone starting on the day of birth, and of C57BL/Tw females given five neonatal injections of 1 microgram DES, 20 micrograms 17 beta-estradiol (E2), 50 micrograms 5 alpha-DHT, 50 micrograms 5 beta-DHT, or the vehicle alone. Ovaries of 30-day-old C57BL mice given five daily injections of 1 microgram DES starting at 3-25 days of age were also examined. PF incidence (% of PF per ovary) and PF frequency (% of mice with PF) were significantly greater in BALB/c mice receiving injections of DES, P, HPC, and T than in the controls. In DES-treated mice at 34 days, PF incidence (2-13 oocytes/follicle) was 120-340 times higher than in the controls. BALB/c mice treated with T, P, and HPC showed PF incidence (two to four oocytes/follicle) three- to six-fold higher than in the controls. In 30-day-old C57BL mice treated with T, E2, and DES, PF incidence also increased by two- to 50-fold. 5 alpha-DHT and 5 beta-DHT failed to increase PF incidence. PF incidence was significantly increased only when neonatal DES treatment was begun on days 0 to 3, but was reduced when started at days 10-25.(ABSTRACT TRUNCATED AT 250 WORDS)     

Concomitant inhibition of pulsatile luteinizing hormone (LH) and stimulation of prolactin release by prostacyclin (PGI2) in ovariectomized (OVX) conscious rats

Prostacyclin (PGI2) or its stable metabolite, 6-keto-PGF1 alpha (1-5 micrograms) in 2.5 microliter 0.05 M phosphate buffer (pH 7.4), was injected into the third ventricle (3 V) of ovariectomized (OVX), freely moving rats. Control animals received 2.5 microliter of buffer. In the initial experiments a control blood sample was taken and then the PGI2 was injected and frequent samples taken thereafter. With this protocol injection of 2 micrograms of PGI2 produced a significant decrease in mean plasma LH only at 60 min after its injection (p less than .05), while the higher dose (5 micrograms) decreased plasma LH concentrations at 30 and 60 min (p less than .01 and p less than .001, respectively). In subsequent experiments, blood was removed from indwelling external jugular vein cannulae every 5-6 min during 2 hours and plasma LH and PRL levels were determined by radioimmunoassay. LH pulses were monitored and several parameters of LH pulsation were calculated during the hour before and after injection of phosphate buffer, PGI2 or 6-keto-PGF1 alpha. Intraventricular injection of phosphate buffer failed to modify the characteristic pulsatile release of LH and did not alter plasma PRL levels. The amplitude of LH pulses was significantly reduced by PGI2 and the inhibitory effect was dose-related. Even a dose of 1 microgram produced a significant reduction in pulse height and the response was graded with maximal reduction occurring with the 5 microgram dose which essentially abolished the LH pulses. Following the microinjection of 6-keto-PGF1 alpha, no significant changes were observed in plasma LH values and the pulses of the hormone. Five micrograms PGI2 considerably elevated plasma PRL values during the 20-25 min following its 3V injection, whereas the same dose of 6-keto-PGF1 alpha produced only a very slight stimulatory effect. Since PGI2 had no effect to alter LH release by cultured pituitary cells in vitro, it is concluded that PGI2 can act on structures near the 3V to inhibit pulsatile release of LHRH.     

Thyrotropin-releasing hormone (TRH) is not thyrotropic but somatotropic in fed and starved adult chickens.

Adult fed and starved Warren chickens, 2 yr of age, and approaching the end of the second laying year, were injected iv with 1 of the following products: 10 micrograms of thyrotropin releasing hormone (TRH); 100 micrograms of bovine thyrotropin (bTSH); 100 micrograms of ovine growth hormone (oGH); saline. The influence on plasma concentrations of thyroxine (T4), triiodothyronine (T3) or chicken GH (cGH) were followed. Prior to injection, it was clear from the control values that starvation for 3 d decreased plasma levels of T3 and increased cGH, whereas 7 d of fasting increased T4 and cGH. The plasma levels of cGH were elevated greater than 10-fold at 15 min following the TRH challenge in food-deprived chickens compared to a less than 4-fold increase in normal fed hens. This increase was followed by a rise in T3 after 1 h, which was also more pronounced in the starved animals, whereas T4 decreased or remained unaffected. Increases in T4 can, however, be obtained with 100 micrograms TSH in normal fed (2-fold) or starved animals (greater than 3-fold). Following injection of 100 micrograms oGH, a significant increase in T3 levels was observed which in fed animals was already present at 30 min, but the higher levels persisted for 1 and 2 h in fed and starved hens. At the same time, a decrease in T4 was observed in both groups of GH-treated chickens. It is concluded that TRH at the dose used is not thyrotropic but has a somatotropic effect and is responsible for the peripheral conversion of T4 into T3.     

Thyroid hormone effects upon Na+K+ dependent adenosine triphosphatase activity of microsomal fraction of liver, muscle and brain of toad Bufo melanostictus

Na+K(+)-ATPase activity in the liver and muscle microsomal membranes have been determined by different doses (0.1, 0.25, 0.5, 1 and 2 micrograms/gm of body weight) of L-triiodothyronine and L-thyroxine in the toad, Bufo melanostictus. The minimum effective dose of T3 was 0.5 microgram/g in case of both liver and muscle to stimulate the enzyme activity and there was dose dependent rise between T3 at the doses of 0.5 and 1 microgram/g. T3 at the doses of 1 and 2 micrograms/g produced more or less the same level of activity. T4 showed an increased activity at 1 and 2 micrograms/g without any dose dependent fashion in the two organs. The doses 0.1 and 0.25 microgram/gm body weight of T3 and 0.1, 0.25 and 0.5 microgram/gm body weight of T4 remained ineffective to elicit any response in both organs. The grain showed no significant change in the enzyme activity at any of the applied doses of T3 and T4. Cycloheximide inhibited T3 induced rise in Na+K(+)-ATPase activity of liver and muscle. Treatment with propylthiouracil caused a significant fall in Na+K(+)-ATPase activity of liver and muscle and the normal value was restored in the two organs after three consecutive injections of T4 at the dose of 1 microgram/g.     

Exercise effects on chromium excretion of trained and untrained men consuming a constant diet

Chromium excretion of eight trained and five sedentary men was determined on rest days and after exercise to exhaustion at 90% of maximum O2 consumption (VO2max) to determine if degree of physical fitness affects urinary Cr losses. Subjects were fed a constant daily diet containing approximately 9 micrograms Cr/1,000 kcal. VO2max of the trained runners was in the good or above range based on their age and that of the sedentary subjects was average or below. While consuming the control diet, basal urinary Cr excretion of subjects who exercise regularly was significantly lower than that of the sedentary control subjects, 0.09 +/- 0.01 and 0.21 +/- 0.03 microgram/day (mean +/- SE), respectively. When subjects consumed self-chosen diets, basal urinary Cr excretion of the trained subjects was also significantly lower than that of the untrained subjects. Daily urinary Cr excretion of trained subjects was significantly higher on the day of a single exercise bout at 90% VO2max compared with nonexercise days, 0.12 +/- 0.02 and 0.09 +/- 0.01 microgram/day, respectively. Urinary Cr excretion of sedentary subjects was not altered after controlled exercise. These data demonstrate that basal urinary Cr excretion and excretion in response to exercise are related to VO2max and therefore degree of physical fitness.     

Bronchodilator drugs and their combinations antagonize the dose-related leukotriene D4-induced airway obstruction in guinea pigs

The effects of theophylline (THEO), terbutaline (TER), and ipratropium bromide (IPRA), given i.v. alone or in combination, were studied on leukotriene D4 (LTD4)-induced airway obstruction in anaesthetized guinea pigs. LTD4 (0.1-1.6 microgram/kg i.v.) obstructed small airways more than large ones as assessed in terms of relative changes of lung resistance (RL) and dynamic lung compliance (CDyn). A slight tachyphylaxis to LTD4 was observed after repeated administration, especially in the responses of large bronchi. The airway effects of LTD4 were almost totally abolished by prior administration of indomethacin (5 mg/kg i.v.) suggesting a central role of secondarily released cyclo-oxygenase products in this model. THEO (1 to 20 mg/kg) and TER (10 to 400 micrograms/kg) antagonized dose-dependently the LTD4 (0.4 microgram/kg i.v.) induced rise in RL and decrease in CDyn, whereas IPRA (10 to 400 micrograms/kg) failed to show comparably activity. THEO 5 and 20 mg/kg proved highly efficient also on the dose-related airway challenge by LTD4 (0.6 and 1.5 microgram/kg i.v.). Combined treatment with THEO 5 mg/kg + Ter 80 micrograms/kg resulted in an additive effect on RL and CDyn. The combination to THEO 20 mg/kg + TER 80 micrograms/kg was about as effective as THEO 20 mg/kg alone suggesting a nearly maximal effect by the latter treatment. It is concluded that THEO is considerably more efficient on the LTD4-induced airway obstruction than previously observed on the cholinergic model in guinea pigs. Combined treatment with THEO and beta 2-adrenoceptor agonist may antagonize in an additive manner the LTD4 effects on large and small airways.     

Glutathione correlates with lipid peroxidation in liver mitochondria of triiodothyronine-injected hypophysectomized rats

The temporal relationship of changes in state 3 respiration, lipid peroxidation, and glutathione (GSH) content was investigated in liver mitochondria of hypophysectomized rats after an injection of 3,3',5-triiodo-L-thyronine (T3). Lipid peroxidation induced by ADP/Fe3+/NADPH was determined by the amount of malondialdehyde formed. Hypophysectomy decreased respiration and lipid peroxidation (from 19.88 +/- 3.04 to 14.19 +/- 1.14 nmol malondialdehyde.mg protein-1.10 min-1) but increased GSH content (from 7.06 +/- 2.08 to 12.46 +/- 3.58 nmol/mg protein). Daily injections of a low dose (5 micrograms/100 g) of T3 for 7 days restored the parameters. Time course (up to 96 h) of these changes was followed after one injection of a moderate (100 micrograms/100 g) and high (1000 micrograms/100 g) dose of the hormone. Respiration showed a significant increase at 24 h and declined slightly at 96 h. There was a slow loss of respiratory control ratio after 24 h. Lipid peroxidation remained unchanged at 24 h and showed a gradual increase, becoming significantly higher at 72-96 h depending on the hormone dosage. Changes in GSH content followed a time course similar to that of lipid peroxidation except that it showed a decrease instead of an increase. There was a high degree of inverse linear correlation between lipid peroxidation and GSH (correlation coefficient = 0.95). Because GSH is required for detoxification of hydroperoxides generated by the respiratory chain, it is suggested that lipid peroxidation may play a major role in the modulation of intramitochondrial GSH.     

Intravital microscopy: a new in vivo technique for visualizing and quantifying effects of regulatory peptides on choledochoduodenal junction motility

Using intravital microscopy, we studied the in vivo effects of regulatory peptides on choledochoduodenal junction motility in guinea pigs. During basal and hormone-stimulated periods, intravital microscopy documented rhythmic, asymmetrical, "milking" contractions of the sphincter ductus choledochi (SDC) which occurred independent of sphincter ampullae (SA) contractions or were followed by SA contractions. Cholecystokinin octapeptide (CCK-8) (greater than or equal to 0.01 micrograms/kg) increased the frequency of SDC contractions and at higher doses (greater than or equal to 0.1 microgram/kg) increased the frequency of SA contractions. Pentagastrin (greater than or equal to 1.0 microgram/kg) and secretin (10 micrograms/kg) decreased the contraction frequencies of both sphincters. Biliary manometry demonstrated similar effects of these peptides on the frequency of the SDC and SA contractions, but also showed that CCK-8 (0.1 microgram/kg) increased the amplitude of SDC and SA contractions while pentagastrin (1 microgram/kg) decreased the amplitude of only SDC contractions. Tetrodotoxin and atropine did not affect hormone-induced changes in frequency, but tetrodotoxin reduced the increase in amplitude of contraction caused by CCK-8. We concluded that intravital microscopy provides a sensitive, in vivo technique to visualize and quantify the complex motility of a small structure like the choledochoduodenal junction.     

The influence of beta-endorphin on testicular endocrine function in adult rats.

The role of beta-endorphin in testicular steroidogenesis is poorly understood. To address this issue, we treated adult hypophysectomized rats intratesticularly with either saline-50% polyvinylpyrrolidone (SAL-PVP) or human beta-endorphin (0.5 microgram/testis; a total of 1 microgram/rat/day) in SAL-PVP for 3 days. Testicular injections were made under ether anesthesia. On Day 3, rats also received injections (s.c.) of either SAL-PVP or 5 micrograms beta-endorphin in SAL-PVP to minimize the dilution of ether in the testis. One hour later, rats were treated (i.p.) with either saline or ovine LH (25 micrograms/rat). One hour after saline or LH injection, blood was obtained via heart puncture for determination of plasma progesterone (P), androstenedione (A-dione), and testosterone (T) levels. The effects of beta-endorphin (50 ng, equivalent to 13.9 pM; or 250 ng, equivalent to 69.6 pM) on P and androgen secretions in vitro were also examined. Intratesticular injections of beta-endorphin significantly (p less than 0.025) decreased the T response to LH treatment, but failed to affect plasma P and A-dione levels. Response of P to LH treatment was increased (p less than 0.005) in medium containing testicular fragments exposed to 250 ng (69.6 pM) beta-endorphin. However, beta-endorphin attenuated LH effects on A-dione and T production in vitro. These studies demonstrate that beta-endorphin inhibits T secretion, possibly because of its effect on the synthesis of T precursors. Thus, testicular beta-endorphin modulates the endocrine function of the testis in adult rats.     

Induction of thyroid hormone in changing Na+K(+)-ATPase activity in different organs of toad, Bufo melanostictus

Single injection of T3, at the doses of 0.5 and 1 micrograms/g body weight, stimulated Na+K(+)-ATPase activity of crude liver homogenate of toad in a dose dependent fashion. Lowering the dose of T3 to 0.25 micrograms/g had no effect on the enzyme activity. T3 at the dose of 2 micrograms/g showed the same level of enzyme activity at par with that of 1 microgram/g. Na+K(+)-ATPase activity of muscle increased with T3 at the doses of 1 and 2 micrograms/g, but without any dose dependent manner while T3 at the doses of 0.25 and 0.5 micrograms/g remained unresponsive in changing the enzyme activity. T4, after 3 consecutive injections, increased the enzyme activity in liver with 1 and 2 micrograms/g and in muscle with 2 micrograms/g only while the other doses of T4 (0.25 and 0.5 micrograms/g in case of liver and 0.25, 0.5, and 1 micrograms/g in case of muscle) had no effect on the enzyme activity. Brain showed no alteration to Na+K(+)-ATPase activity with the same doses of T3 and T4. Cycloheximide counteracted the T3 induced rise in enzyme activity. The reduced level of Na+K(+)-ATPase activity in the PTU treated toad was recovered and brought to the control level after 3 consecutive injections of T4 at the dose of 1 microgram/g.     

Autonomic effects of central injections of D-Ala2-Met-enkephalinamide (DAME) in the conscious monkey

The use of naloxone (NAL), an opioid receptor antagonist, has provided indirect evidence that endogenous opioids contribute to cardiovascular depression during shock. To determine if endogenous opioids act centrally to influence cardiovascular function, injections of D-Ala2-Met-enkephalinamide (DAME), a potent Met-enkephalin analog, were made into the 3rd cerebral ventricle (ICV) of 5 conscious cynomulgus monkeys restrained in primate chairs. Systolic blood pressure (SBP) and heart rate (HR) were determined every 10 min during a 30-60 min control period and for up to 5 hr post-injection. Colonic temperature (Tc) was monitored continuously. SBP declined from baseline values with 50 and 100 micrograms (85.2 and 170.4 nM) doses but was significant (p less than 0.001) for only the 100 micrograms dose between 15-125 min post-injection. HR also decreased but did not exhibit any significant variation with time. However, when averaged across time, HR fell significantly (p less than 0.001) from baseline: -9.1 +/- 2.3 and -15.0 +/- 2.1 b/min for 50 and 100 micrograms DAME, respectively. Tc displayed a nonsignificant, delayed (greater than 2 hr) rise in Tc with the 50 micrograms dose, whereas the 100 micrograms dose caused a significant (p less than 0.001) decline in Tc (from 65-125 min post-injection). NAL injected ICV attenuated the effects of DAME but had no effect on SBP, HR or Tc when injected alone. Systemic injection of DAME (300 micrograms) in one monkey produced a transient decline in SBP (26 mmHg within 2 min) which returned to baseline values 4 min post-injection. HR and Tc were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)