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1.
The highest values of gamma-aminobutyric acid (GABA) in the genital tract of the rat at different stages of the oestrous cycle were found in the oviduct (3.5-7 micrograms/mg protein) and the lowest in the ovary (50-100 ng/mg protein). The values for uterus and vagina ranged between 80 and 150 ng/mg protein. GABA (10-30 ng/microliter) was also found in fluid in the ovarian bursa. At 11:00 h, on the day of oestrus, GABA content increased in the ovaries but values in the oviducts were maximal at 11:00 h on the day of pro-oestrus. Variations in GABA content of the vagina were also found. Uterine cervix or uterine horn showed no changes during the oestrous cycle. The GABA content was not uniform throughout the oviduct: the highest values were found in the portion next to the ovary. At 10 days after removal of the right oviduct, GABA values in the ovary and ovarian bursa fluid decreased on the operated side. At 1 month after surgery, the values in ovary were normal but the values in ovarian bursa fluid were still low, suggesting that the source of ovarian GABA was not the oviduct. The variations observed in the present paper suggest an involvement of GABA in reproductive physiology.  相似文献   

2.
The occurrence and the localization of 4-aminobutyrate:2-oxoglutarate transaminase (GABA-transaminase) in the non-pregnant and pregnant rat oviduct were examined using biochemical and enzyme histochemical techniques. Specific GABA-transaminase activity was detected in the ampullary and isthmic portions of the oviduct as well as in the utero-tubal junction. The enzymic activity was lower in the ampullary than in the isthmic or intramural segments of the oviduct. Pregnancy induced a significant increase of GABA-transaminase activity in each portion of the oviduct. Enzyme histochemistry showed the highest GABA-transaminase reactivity at the level of the epithelial cells of the oviduct irrespective of the portion of the tube examined. A faint specific activity was demonstrated in the smooth muscle of the oviduct while the serosa did not show specific staining. Our findings indicate that: the observed increase of GABA-transaminase activity in the oviduct of the pregnant rat may be responsible for the reduced GABA levels in the oviduct during gestation; and the extraneuronal localization of GABA-transaminase activity does not seem to support the suggestion of a possible GABAergic innervation of the oviduct.  相似文献   

3.
The developmental pattern and distribution of peptide-containing neurons in the rat heart right atrium has been studied by indirect immunofluorescence. Antibodies against neuropeptide Y (NPY), substance P (SP), and vasoactive intestinal polypeptide (VIP) were applied to whole-mount stretch preparations of the right atria from hearts of newborn to 40-day-old animals. NPY-like immunoreactivity (LI) was compared with the synaptic vesicle marker SV2 in double immunoincubation studies. The distribution of immunofluorescence was studied by confocal laser scanning microscopy. NPY-LI and SP-LI were present throughout the atria already at birth, in contrast to VIP-LI that was observed at day 10. The postnatal changes of innervation were basically quantitative, with an increase in density of nerve fibres and number of varicosities, while the basic pattern of innervation was essentially established during the first 1–10 days. NPY- and SP-positive bundles of fibres appeared to enter the right atrium along the superior caval vein, having extrinsic origins. Nerve fibres with NPY-LI colocalized in most nerve terminals with SV2-LI, and showed a developmental pattern similar to that observed for adrenergic neurons earlier. These NPY/SV2 positive fibres probably represent the extrinsic NPY innervation. In addition, NPY-LI was identified in large intrinsic nerve cells bodies located near the atrioventricular (AV) region. Most of the VIP-LI was observed in short nerve fibres originating in intrinsic VIP-positive cell bodies, but a few apparently extrinsic VIP-positive fibres were found, probably representing preganglionic parasympathetic neurons. SP in the atria was probably of extrinsic (sensory) origin and no nerve cell bodies with SP-LI were detected. The results show that the peptidergic innervation in the developing rat right atrium involves both extrinsic and intrinsic peptidergic neurons which may participate in the regulation of neurotransmission in local neuronal circuits.  相似文献   

4.
The objective of this study was to examine the effects of two different denervation procedures on the distribution of nerve fibers and neurotransmitter levels in the rat jejunum. Extrinsic nerves were eliminated by crushing the mesenteric pedicle to a segment of jejunum. The myenteric plexus and extrinsic nerves were eliminated by serosal application of the cationic surfactant benzyldimethyltetradecylammonium chloride (BAC). The effects of these two denervation procedures were evaluated at 15 and 45 days. The level of norepinephrine in whole segments of jejunum was initially reduced by more than 76% after both denervation procedures, but by 45 days the level of norepinephrine was the same as in control tissue. Tyrosine hydroxylase (nor-adrenergic nerve marker) immunostaining was absent at 15 days, but returned by 45 days. However, the pattern of noradrenergic innervating axons was altered in the segment deprived of myenteric neurons. Immunohistochemical studies showed protein gene product 9.5 (PGP 9.5)-immunoreactive fibers in whole-mount preparations of the circular smooth muscle in the absence of the myenteric plexus and extrinsic nerves. At 45 days, the number of nerve fibers in the circular smooth muscle increased. Vasoactive intestinal polypeptide (VIP)-immunoreactive fibers, a subset of the PGP 9.5 nerve fibers, were present in the circular smooth muscle at both time points examined. Choline acetyltransferase (CAT) activity and VIP and leucine enkephalin levels were measured in separated smooth muscle and submucosa-musosal layers of the denervated jejunum. VIP and leucine-enkephalin levels were no different from control in tissue that was extrinsically denervated alone. However, the levels of these peptides were elevated two-fold in the smooth muscle 15 and 45 days after myenteric and extrinsic denervation. In the submucosa-mucosa, VIP and leucine enkephalin levels also were elevated two-fold at 15 days, but comparable to control at 45 days. CAT activity was equal to control in the smooth muscle but elevated two-fold in the submucosa-mucosa at both times. These results provide evidence for innervation of the circular smooth muscle by the submucosal plexus. Moreover, these nerve fibers originating from the submucosal plexus proliferate in the absence of the myenteric plexus. Furthermore, the myenteric neurons appear to be essential for normal innervation of the smooth muscle by the sympathetic nerve fibers. It is speculated that the sprouting of the submucosal plexus induced by myenteric plexus ablation is mediated by increased production of trophic factors in the hyperplastic smooth muscle.  相似文献   

5.
Some biochemical characteristics of L-glutamate decarboxylase (GAD) were compared using crude homogenates of the rat oviduct, ovary, and hypothalamus. As estimated by the measurement of CO2 production, the specific activities of oviductal and ovarian GAD were about 10 and 3% of the hypothalamic value, respectively. Stoichiometric formation of gamma-aminobutyric acid (GABA) and CO2 from L-glutamate could be observed in oviduct and hypothalamus, while in ovarian homogenates the production of CO2 was more than nine times that of GABA. Hypothalamic and tubal GAD showed similar time course, temperature dependence, and pH dependence. The dependence on protein concentration and on exogenous cofactor supply was also similar in these two tissues. The kinetic constant for L-glutamate as a substrate was nearly the same in oviduct (1.30 mM) and hypothalamus (1.64 mM). The responsiveness of tubal and hypothalamic GAD to various inhibitors was also similar. The present findings indicate that the oviductal and the hypothalamic GAD may be identical, and they suggest a possible GABAergic innervation of the Fallopian tube.  相似文献   

6.
gamma-Aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD) activities were measured in the ovary and the Fallopian tube of rats and compared with brain values. GABA levels in the Fallopian tube were about twice as high as in the brain, while in the ovary they represented only about 5% of the amino acid content of the CNS. In vitro decarboxylation of glutamate, measured via CO2 formation, occurred both in the Fallopian tube and in the ovary. These two organs contained, respectively, 10% and 1% of brain GAD activity. However, the actual formation of GABA from glutamate in a high-speed supernatant was detectable only in the Fallopian tube, where it represented about 5% of brain GAD activity. In contrast with the enzyme present in ovary, liver, anterior pituitary, and kidney, that in the Fallopian tube was quantitatively precipitated by a specific antiserum directed against rat neuronal GAD. Moreover, subcutaneous transplantation resulted in a quantitative decrease of both GABA levels and GAD activity in the Fallopian tube while no change occurred in the ovary, and vagus nerve section induced a 50% decrease of GAD activity in the Fallopian tube, although GABA levels were not significantly altered. The findings suggest an extrinsic GABAergic innervation in the rat Fallopian tube but not in the ovary.  相似文献   

7.
An enzymatic microassay method for glutamate decarboxylase (GAD) and gamma-aminobutyric acid (GABA) was improved to yield a high sensitivity and a low blank. The 20-microns thick freeze-dried sections (0.2-1.5 micrograms dry weight) were prepared from the oviduct and ovary of rat. The analysis of these microsamples by the improved method showed that, contrary to the previous observations, the rat ovary is devoid of GAD activity and contains a trace amount of GABA. Both are present abundantly in the oviduct. In the oviduct mucosa, significant GAD activity was found in the estrous phase, whereas the activity was nearly null during other phases of the estrous cycle. GABA concentration in the oviduct mucosa was 10-fold higher than in the cerebral cortex; its variation during the estrous cycle was not remarkable. In the muscle layer of oviduct, GAD activity had a low peak in the estrous phase and GABA concentration was almost constant during the estrous cycle. The denervation experiment showed that GAD is present in the nerve terminals innervating the oviduct.  相似文献   

8.
Evidence thatl-glutamate is a neurotransmitter of corticofugal fibers was sought by measuring changes in several biochemical markers of neurotransmitter function in discrete regions of spinal cord after ablation of sensorimotor cortex in monkeys. One and five weeks after unilateral cortical ablation, samples from six areas of spinal cord (ventral, lateral and dorsal regions of the left and right sides) were analysed for choline acetyltransferase (ChAT) activity and contents of amino acid transmitter candidates-glutamic acid (Glu), aspartic acid (Asp), glycine (Gly), taurine (Tau) and -aminobutyric acid (GABA). During one to five weeks after unilateral cortical ablation of the monkey, prolonged hemiplegia in the contralateral side was observed. Histological examination of the spinal cord 5 weeks after unilateral (left) cortical ablation showed no apparent change in either control (ipsilateral, left) or affected (contralateral, right) sides of the cord as examined by the Klüver-Barrera method. The ChAT activity as a cholinergic marker was scarcely changed in any region of either left (control) or right (affected) side of the spinal cord at one and five weeks after unilateral (left side) ablation of the motor cortex. Amino acid levels in each region of the spinal cord were not significantly changed one week after unilateral ablation of the motor cortex. However, a significant decrease of Glu content was observed in the lateral column of the affected (right) side compared to the control (left) side of cervical and lumbar cord five weeks after cortical ablation of the left motor area. No concomitant alterations of other amino acids were detected. These data strongly suggest thatl-Glu is a neurotransmitter for corticofugal pyramidal tract fibers to anterior horn secondary neurons related to motor control activity in monkey spinal cord.  相似文献   

9.
Plantaris muscle hypertrophy resulting from surgical ablation of the synergistic gastrocnemius muscle was compared between nontumor- and GH3 tumor-bearing rat groups (n = 8-10). GH3 cells (10(6)) were subcutaneously injected into 150-g female Wistar-Furth rats to initiate the tumor. After 17 days, the tumor-bearing rats gained 5.7 g body wt/day compared with 2.0 for the nontumor-bearing rats. The left gastrocnemius muscle was surgically removed from both nontumor and tumor groups. The gastrocnemius was removed from the tumor group after an increased growth rate was achieved. Seven days after surgery, the animals were killed and plantaris muscles were removed. The wet weight of the left plantaris muscle increased 45.6 and 44.0% over the unoperated contralateral control (right side) in the nontumor and tumor groups, respectively. The right control plantaris muscle in the tumor group was 63% heavier than the right control plantaris from the nontumor group; however, the proportion of body weight for plantaris was similar between the two groups. The effect of gastrocnemius ablation and tumor treatment on plantaris weight was additive, and the percent increase over the unoperated contralateral control side was similar between the two groups. These data demonstrate that skeletal muscle hypertrophy occurs in adult animals in which growth has been stimulated by a growth hormone-secreting tumor and could suggest that the muscle growth response caused by the tumor is operating by a mechanism different than work-induced hypertrophy.  相似文献   

10.
Summary The effect of unilateral adrenalectomy on the incorporation of tritiated leucine into the ventromedial nucleus of both sides of the rat hypothalamus was studied by light- and electron-microscopical autoradiography. The left adrenal had been removed and 14 days later labeled amino acid was given intravenously. Rats were killed 5, 30, 60 and 120 min after isotope administration. Following unilateral adrenalectomy there is a marked difference in the autoradiographic reaction of both sides of the hypothalamic ventromedial nucleus. On the right side the number of autoradiographic silver grains is much higher than on the left side, the difference being statistically significant for each animal and for each time interval. In accordance with previous findings the data suggest the existence of a neural pathway from the adrenal gland to the hypothalamus.  相似文献   

11.
Quail eggs were injected on Day 10 of incubation with 0, 5, 10, 20 or 40 micrograms oestradiol benzoate. Females hatching from these eggs were reared on a 16L: 8D photoperiod and egg laying was recorded. Blood samples were taken at 37, 40, 43, 46, 49, 52, 55, 58 or 61 days of age and LH concentrations were measured by a double-antibody radioimmunoassay. Birds were killed at 61 days of age; ovaries and oviducts were weighed and examined. Egg laying was greatly reduced by oestradiol benzoate treatment, but for birds that did lay, age at first oviposition was normal. LH levels were not affected by oestradiol benzoate treatment, and were highest at 40 and 49 days of age. Oestradiol benzoate had no effect on ovarian weight, number of follicles with diameter greater than 1 cm, or number of post-ovulatory follicles. Oestradiol benzoate had a dose-related effect on the likelihood that females would have two oviducts, and for those females that had retained the right oviduct, the left oviduct was smaller than normal. Oestradiol benzoate-treated females were more likely to have ovulated yolks in the body cavity. Embryonic treatment with oestradiol benzoate therefore appears to inhibit egg laying by causing oviduct abnormalities, rather than by (as happens in mammals) inhibiting ovulation.  相似文献   

12.
The GABAergic regulation of proopiomelanocortin messenger RNA (POMC mRNA) levels in rat pituitary was investigated using molecular hybridization of DNA complementary to POMC mRNA. Endogenous GABA levels increased, in vivo, by inhibiting the GABA catabolic enzyme GABA-transaminase (GAT) with ethalonamine-O-sulfate (EOS) or with vinyl-GABA (VG). Rats were treated with VG (100 mg/kg or 800 mg/kg) or EOS (100 mg/kg), administered each second day. GABA levels in the neurointermediate lobe (NIL) and anterior lobe (AL) of the hypophysis and in the hypothalamus were significantly increased following 4 days of VG treatment (800 mg/kg). All treatments resulted in a 40-60% decrease in POMC mRNA levels after 4 days in the NIL but not in the AL. A similar decrease of about 60% in POMC mRNA levels in the NIL was seen when EOS was given in the drinking water (5 mg/ml). In this set of experiments the time course of alteration of POMC mRNA in the NIL and the concentration of alpha-MSH, a POMC-derived peptide, were analysed. After one day of EOS treatment, when POMC levels had already decreased by 40%, alpha-MSH levels were significantly elevated (34% above controls), possibly reflecting an inhibition of alpha-MSH secretion. However, after 4 and 8 days, POMC mRNA levels and tissue alpha-MSH levels had significantly decreased. When tested in vitro, on primary cultures of IL cells, GABA (10 microM) reduced POMC mRNA levels by 40% after 3 days of treatment. These results show that GABA exerts a direct inhibitory effect on POMC gene expression in the intermediate lobe.  相似文献   

13.
Changes in content of selected neuroactive amino acids [glutamic acid, aspartic acid, glycine, gamma-aminobutyric acid (GABA) and taurine] and acetylcholine (ACh) in the rat hippocampus following transient forebrain ischemia were investigated using male Wistar rats. Rats were allowed to survive for 1 or 5 days following 10 or 20 min of 4-vessel occlusion, and killed by a focused microwave irradiation. A significant reduction in all neuroactive amino acids examined except GABA was noted in the hippocampus on the fifth day. One day after the 4-vessel occlusion for 10 min, no significant effect on the content of neuroactive amino acids in all brain areas was observed. gamma-Aminobutyric acid content in the hippocampus was only significantly reduced on the fifth day after the occlusion for 20 min. Similarly, a significant decrease in ACh content in the hippocampus was observed on the fifth day after the occlusion for 20 min. Considering the data that a significant loss of neuronal cells in the hippocampus (delayed neuronal death) was detected only 5 days after the 4-vessel occlusion, it can be said that the alterations in the hippocampus of neuroactive amino acids such as glutamic acid, aspartic acid, glycine and taurine are more sensitive than those in GABA and ACh against cerebral ischemia. A possible correlation of these changes of neuroactive amino acids in the occurrence of delayed neuronal death in the hippocampus is also suggested.  相似文献   

14.
The effect of administration of chlorpromazine on the activity of glutamine synthetase and glutaminase and the content of glutamate and gamma-aminobutyric acid (GABA) in different regions of rat brain was studied in an investigation of the possible role of these amino acids in the lowering of the seizure threshold following prolonged administration of chlorpromazine. Chlorpromazine was administered at a dose of 20 mg/kg of body weight s.c. For the acute study, the animals were killed 20 min after a single injection. For the long-term study, the animals were treated every day with the same dose for 21 days and were killed 20 min after the last injection. The results showed an increase in glutamate level in each brain region investigated following long-term administration, but only in the cerebral cortex after a single dose. GABA levels showed an increase in the brainstem only in acute experiments. Glutamine synthetase activity was increased in all three regions after a single dose and only in cerebral cortex after long-term administration. Glutaminase activity showed a decrease in cerebral cortex only after long-term administration of the drug. These results suggest the possible occurrence of a state of increased excitability in the brain as a result of long-term administration of chlorpromazine, thus contributing to the known complication of seizures.  相似文献   

15.
Immature female rats (60-65 g) were injected with 4 i.u. PMSG on Day -2, and allocated to 3 groups. For Groups I and II, unmated donors were killed 67-69 h after PMSG injection, shortly after the expected time of ovulation. Oocytes were recovered from the oviducts and transferred immediately into the oviduct of mated recipients (Group I) whose ipsilateral ovary had been exposed by peeling back the bursa, preventing endogenous oocytes from entering the oviduct, or were fertilized in vitro (Group II) and were transferred 16-18 h later. Rats in Group III were allowed to mate and half were killed 6 h after mating. The fertilized oocytes were then incubated for 10-12 h until transfer. The remaining rats in Group III were killed 16-18 h after mating and fertilized oocytes were collected and transferred immediately. Recipient rats were killed on Days 2, 5, 8 and 20. Zygotes resulting from in-vitro fertilization (Group II) were as able as those fertilized in donors (Group III) or recipients (Group I) to develop to the 2-cell stage, but underwent significantly greater embryonic loss beyond this stage of development. There was a slower rate of development of such oocytes to the blastocyst stage (Day 5) and a lower mean weight of implantation sites (Day 8). Transfer of zygotes after in-vitro fertilization resulted in a loss of 35% of the embryos at the time of implantation. These results suggest that in-vitro fertilization of rat oocytes leads to defects in the embryos causing a delay in early embryo development and a large number of implantation losses.  相似文献   

16.
The effect of hornet venom sac extract (VSE) on hepatic function in rats was evaluated by measurement of bile acid (BA) levels. A significant dose-dependent elevation of BA in rat serum upon repeated VSE administration was found. Rats envenomed for 2 weeks showed a significant rise of serum BA compared with the controls or with rats envenomed for 6 days. In rats envenomed for 1 week and killed after another week without envenomation, an improvement of the biochemical status was observed. These observations demonstrated that BA levels reflect the VSE-induced hepatic injury. They suggest that the cholestatic effects of VSE may be due to an impairment of bile acid excretion, but the elevations could also reflect parenchymal hepatic injury.  相似文献   

17.
We showed previously that the vasopeptidase inhibitor (VPI) omapatrilat improves peri-myocardial infarction (MI) survival, but the mechanisms involved and whether these effects are sustained remained to be determined, and are the subject of this study. Rats (n = 272) received omapatrilat (20 mg x kg-1x day-1) starting 7 days before MI and continued peri- and post-MI, or no treatment (control). One group of rats had continuous ambulatory ECG and blood pressure recordings started 6 h before MI and continued until 24 h after MI, when survival was evaluated, and the rats were killed, and MI size was evaluated. A second group had left ventricular (LV) remodeling evaluated by echocardiography at 30 days and, at 38 days, had cardiac hemodynamics and morphology done and survival evaluated. Survival 24 h after MI (n = 255) improved with omapatrilat (60% vs. 46% for control; P = 0.0378). Over the next 37 days, there was no further improvement with omapatrilat but the early benefit was sustained. Omapatrilat reduced MI size 24 h after MI (36 +/- 2 vs. 42 +/- 2 mm2 for controls; P = 0.034). Omapatrilat reduced ventricular arrhythmia score 1-12 h after MI. Omapatrilat decreased blood pressure, but not during the first 24 h after MI. Omapatrilat reduced LV diastolic and systolic dimensions and LV and right ventricular weights compared with control large MI, indicating a decrease in reactive hypertrophy. Improvement in cardiac remodeling was accompanied by improved cardiac hemodynamics. Thus this study indicates that pre-, peri-, and post-MI treatment with the VPI omapatrilat is beneficial in survival, ventricular arrhythmias, LV remodeling, and cardiac function.  相似文献   

18.
Rats were given γ-vinyl GABA (4-amino-hex-5-enoic acid), a new irreversible inhibitor of GABA aminotransferase (GABA-T), by daily subcutaneous injection (100mgkg) for 11 days. Amino acids were quantitated in the brains of the γ-vinyl GABA-treated and control animals 24 h after the last injection, and enzyme activities of GABA-T and glutamic acid decarboxylase (GAD) were measured. Chronic administration of γ-vinyl GABA produced a 150% increase in brain GABA content, along with marked increases in the contents of B-alanine and homocarnosine. Brain GABA-T activity was reduced by 26%, and GAD activity was reduced by 22%. In addition, γ-vinyl GABA caused a marked increase in hypotaurine content in rat brain, suggesting that it acts as an inhibitor of hypotaurine dehydrogenase, and it produced significant decreases in brain contents of glutamine and threonine. Although it is an effective GABA-T inhibitor, γ-vinyl GABA apparently affects several other brain enzymes as well, and it may not be an ideal drug for elevating brain GABA levels in man.  相似文献   

19.
Summary The distribution of L-glutamate decarboxylase (GAD), a major biosynthetic enzyme for gamma-aminobutyric acid (GABA), was examined in the oviduct and ovary of the rat by means of an immunohistochemical technique. The polyclonal antiserum raised against brain GAD showed specific immunoreaction in some non-neuronal elements of the sex organs. In the oviduct, the inner layer of the mucosa was predominantly labelled. The selective distribution of GAD immunoreactivity in epithelial cells of the oviduct is consistent with former findings for GABA-like immunoreactivity in the same organ, indicating that the GAD-catalyzed reaction may be a major biosynthetic pathway for GABA even in these cells. In the ovary, vacuole-like formations within the follicular fluid and oocytes showed intense, specific staining. The occurrence of GAD immunoreactivity inside developing ovarian follicles including the oocyte may suggest a role for GABA related to follicular development and certain functions concerning the ovum.  相似文献   

20.
Total lipid fatty acid composition was investigated in brain hemispheres of male Spontaneously Hypertensive Rats (SHR), compared with normotensive Wistar Kyoto rats (WKY) used as controls. Both strains were suckled by adoptive Wistar mothers, and then fed a standard diet after weaning. No difference was observed between the two hemispheres of WKY killed either at 10 or 30 days. In SHR killed at 10 days, the two hemispheres showed differences, SHR left hemispheres exhibiting greater fatty acid composition changes than those of WKY, phenomenon that toned down at 30 days. Hence, SHR pups showed a different total lipid fatty acid composition of their brain hemispheres when compared with their WKY controls, though the two strains received the same diet. Genetically programmed hypertension might be, directly or not, involved in these changes.  相似文献   

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