Catecholaminotropic effects of catecholamines in a teleost fish,Anguilla rostrata

Summary Injections of physiological and supraphysiological doses of epinephrine (E) into cardiaccannulated eels cause a dose-related increase of plasma dopamine (DA) and norepineprine (NE) within 3 min. Likewise, both exogenous DA and NE increase the plasma titers of the respective other two catecholamines (CAs). The baseline titers of NE and E are closely correlated. Lack of a correlation of the baseline titers of NE and E with that of DA appears to be due to a faster disappearance rate of DA from the circulation. E is strongly hyperglycemic, and the weaker glycemic action of NE may be mediated via E release. The effects of E seem to depend on a spurt-like increase rather than its titer per se. The ability of the eel to cope with very fast, excessive increases of plasma CAs raises the question of the underlying mechanisms.Abbreviations CA(s) catecholamine(s) - DA dopamine - NE norepinephrine - E epinephrine     

Comparison of the effects of neuropeptide Y and adrenergic transmitters on LH release and food intake in male rats

In view of the recent demonstrations that Neuropeptide Y (NPY) and adrenergic transmitters coexist in neurons of the rat brain, we have compared the effects of intraventricular (Ivt) injections of NPY and catecholamines on LH release and food intake in intact male rats. Of the three catecholamines, dopamine (DA), norepinephrine (NE) and epinephrine (E), only E (5.3 micrograms or 15.9 micrograms/rat) significantly stimulated LH release, although NE and E (5.3 micrograms/rat) were equally effective in eliciting food intake in satiated rats. Ivt administration of 10 micrograms NPY significantly stimulated LH release, whereas either lower (0.5 or 2 micrograms/rat) or higher (25 micrograms/rat) doses were ineffective. In contrast, NPY at doses of 0.5 - 10 micrograms/rat increased cumulative food intake in a dose-related fashion. These findings present preliminary evidence of the physiological correlates of the neuronal coexistence of adrenergic transmitters and NPY in the brain and raise the possibility that NPY may normally act either independently, in concert with or via adrenergic systems to evoke LH release and feeding responses in the rat.     

Effects of exogenous catecholamines on plasma catecholamines and glucose in the sea lamprey,Petromyzon marinus

Summary The effects of exogenous dopamine (DA), norepinephrine (NE) and epinephrine (E) on endogenous catecholamine (CA) titers and glycemia were studied with a highly specific and sensitive radioenzymatic assay (REA) in cardiac-cannulated, prespawning sea lampreys. Neither DA nor NE had a specific effect on the endogenous titers of the other two CAs, or on glycemia. In contrast, E caused a strong increase of both DA and NE at three different doses, one of which must have been in the physiological ranges. This increase may be due to direct stimulation of E on the NE and DA cells. E also caused hyperglycemia 45 min after the injection; however, this effect occurred only with unphysiologically high doses. An estimation of the disappearance rate of exogenous CAs revealed a mammalian-like speed, ranging from 3–5.5 min.Abbreviations CA catecholamines - DA dopamine - E epinephrine - NE norepinephrine - REA radioenzymatic assay     

Liquid chromatography/luminescence techniques

The techniques of pre- and post-column reactions in HPLC with fluorimetric detection for catecholamines (CAs) were described. The post-column reactor based on trishydroxyindole formation have frequently used in the routine analysis of CAs. The fluorescence intensity of the derivative dopamine (DA) at 520 nm (with exitation at 410 nm) is weaker than that of the norepinephrine (NE) and epinephrine (E) derivatives. Although urinary DA can be detected by using this method, its detection in plasma is difficult. Recently a new pre-column derivatization method using 1,2-diphenylethylenediamine (DPE) was found in Ohkura's laboratory. After the clean-up using a cation-exchange column, CAs were converted into the fluorescent compounds by reaction with DPE. The limites of detection for NE, E and DA were about 2 fmol at a signal-to-noise ratio of 2. DA in plasma can be determined by this method. A modified THI technique with electrochemical oxidation was examined. The above methods are very sensitive and selective for the measurement of CAs (NE, E and/or DA) in biological samples.     

Pretraining infusion of DSP-4 into the amygdala impaired retention in the inhibitory avoidance task: involvement of norepinephrine but not serotonin in memory facilitation

The present study investigated the involvement of amygdala noradrenergic (NE) and serotonergic (5-HT) systems in memory storage processing. Rats bearing chronic cannulae in the amygdala were trained on a one-trial inhibitory avoidance task and tested for retention 24 hrs later. Five days prior to training, rats received intra-amygdala infusion of vehicle or various doses of N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP-4)-a NE-specific neurotoxin when given peripherally. Results showed that pretraining intra-amygdala infusion of 10.0 micrograms or 30.0 micrograms of DSP-4 impaired retention. Further, 30.0 micrograms of DSP-4 also abolished the memory enhancing effect of epinephrine (E) injected peripherally. However, local infusion of DSP-4 depleted not only NE but also 5-HT and DA substantially. Subsequent experiments found that the retention deficit induced by 30.0 micrograms of DSP-4 could be ameliorated by 0.2 microgram NE but not by 5-HT at a wide range of doses infused into the amygdala shortly after training, which ascribed the deficit to depletion of NE. After protecting the 5-HT terminals by a pretreatment of fluoxetine (15.0 mg/kg), pretraining intra-amygdala infusion of 30.0 micrograms DSP-4 shifted the memory-enhancing dose of E from 0.1 mg/kg to 1.0 mg/kg. In contrast, pretraining intra-amygdala infusion of 15.0 micrograms 5,7-dihydroxytryptamine (5,7-DHT) or DSP-4 with a pretreatment of desipramine (DMI, 25.0 mg/kgx2) to protect NE terminals failed to impair retention or attenuate the memory enhancing effect of 0.1 mg/kg E injected peripherally. These findings, taken together, suggest that the memory modulatory effect of peripheral E involved, at least partially, the amygdala NE system.     

Physiological doses of epinephrine in the human: chronotropic but not hyperglycemic or catecholaminotropic

Single physiological doses of epinephrine did not affect the blood sugar level of human volunteers though they caused a marked tachycardia that was accompanied by a strong transient sensation, typically described as fullness in the chest. Epinephrine did not cause the release of norepinephrine and/or dopamine in man, in contrast to three other vertebrates (lamprey, eel, and rat). In the human, as in the rat and cyclostomes, the glycemic effect of epinephrine occurs only during stress and/or unphysiological conditions, while the chronotropic effects are probably physiological from cyclostomes to man.     

Plasma dopamine: regulation and significance

Dopamine (DA) normally circulates in plasma. The plasma concentration of the free form of DA is approximately equivalent to that of epinephrine (E) and 20% that of norepinephrine (NE). The free form constitutes less than 2% of total plasma DA, and the remainder exists predominantly as sulfate or glucuronide conjugates. DA is found in adrenal medulla and cortex, peripheral nerves, sympathetic ganglia, carotid body, and kidney, but quantitatively the origin of circulating DA remains poorly understood. Plasma concentrations of free DA increase in association with events that increase sympathetic tone, although to a much lesser degree than seen for NE or E. Thus, upright posture, bicycle exercise, a variety of emotional and physical stresses, and hypoglycemia may be associated with increases in plasma free DA. Plasma DA decreases during the course of dietary sodium depletion in humans, in contrast to the plasma NE response, and consistent with a physiological role for DA in the regulation of aldosterone secretion. Plasma DA increases after administration of its precursor L-dihydroxyphenylalanine, together with the decarboxylase inhibitor carbidopa. Plasma NE and (in some studies) plasma DA decrease after administration of the DA receptor agonist bromocriptine. In contrast, plasma DA and one of its major metabolites, homovanillic acid, increase after administration of the DA receptor antagonist haloperidol. Administration of the endogenous opioid peptide beta-endorphin into the brain increases central sympathetic outflow, thus increasing plasma DA concentration, although to a lesser extent than for NE or E. Disordered basal concentrations of DA in plasma or disordered responses of plasma DA have been reported in a number of disease states. Clear understanding of physiological roles of DA in plasma and of its pathophysiology awaits definition.     

Effect of atropine on plasma gastrin and somatostatin concentrations during sham feeding in man

The purpose of these studies was to measure circulating gastrin and somatostatin concentrations during sham feeding in humans and to evaluate the effect of two doses of intravenous atropine on circulating concentrations of these peptides. Gastric acid and bicarbonate secretion and pulse rate were also measured. Sham feeding increased plasma gastrin concentrations by approximately 15 pg/ml but had no effect on plasma somatostatin-like immunoreactivity (SLI). A small dose of atropine (5 micrograms/kg) augmented plasma gastrin concentrations during sham feeding significantly (P less than 0.01), but did not affect plasma SLI. Atropine also significantly inhibited gastric acid secretion and gastric bicarbonate secretion (by 62% and 52%, respectively), but pulse rate was not affected. A larger dose of atropine (15 micrograms/kg intravenously) suppressed plasma gastrin concentrations significantly compared to the smaller 5 micrograms/kg atropine dose (P less than 0.02), so that plasma gastrin concentrations when 15 micrograms/kg atropine was given were not significantly different from those during the control study. 15 micrograms/kg atropine reduced gastric acid and bicarbonate secretion by 81% and 66%, respectively, and also increased pulse rate by 15 min-1. These studies indicate that small doses of atropine enhance vagally mediated gastrin release in humans, probably by blocking a cholinergic inhibitory pathway for gastrin release. Although the nature of this cholinergic inhibitory mechanism is unclear, we found no evidence to incriminate somatostatin. Our finding that the larger dose of atropine reduced serum gastrin concentrations compared with the smaller dose suggests that certain vagal-cholinergic pathways may facilitate gastrin release.     

The peripheral noradrenergic terminal as possible site of action of salsolinol as prolactoliberin

Salsolinol, an endogenous isoquinoline, induces selective prolactin release in rats [Tóth, B.E., Homicskó, K., Radnai, B., Maruyama, W., DeMaria, J.E., Vecsernyés, M., Fekete, M.I.K., Fül?p, F., Naoi, M., Freeman, M.E., Nagy, G.M., 2001. Salsolinol is a putative neurointermediate lobe prolactin releasing factor. J. Neuroendocrinol. 13, 1042-1050]. The possible role of dopaminergic and adrenergic signal transduction was investigated to learn the mechanism of this action. The effect of salsolinol (10mg/kg i.v.) was inhibited by reserpine treatment (2.5mg/kg i.p.) and reinstated by pretreatment with monoamine oxidase inhibitor (pargyline 75 mg/kg i.p.). Salsolinol did not affect the in vitro release of dopamine (DA) in the median eminence, and did not inhibit the L-DOPA induced increase of DA level in the median eminence. 1-Methyl dihydroisoquinoline (1MeDIQ) is an antagonist of salsolinol induced prolactin release and causes increase in plasma NE level [Mravec, B., Bodnár, I., Fekete, M.I.K., Nagy, G.M., Kvetnansky, R., 2004. An antagonist of prolactoliberine induces an increase in plasma catecholamine levels in the rat. Autonom. Neurosci. 115, 35-40]. Using tissue catecholamine contents as indicators of the interaction between salsolinol and 1MeDIQ we found no interaction between these two agents to explain the changes in prolactin release in the median eminence, lobes of the pituitary, superior cervical and stellate ganglion. Increasing doses of salsolinol caused a dose dependent decrease of tissue dopamine concentration and increase of NE/DA ratio in the salivary gland, atrium and spleen. These changes of DA level and NE/DA ratio run parallel in time with the increase of prolactin release. 1MeDIQ antagonized the increase of prolactin release and decrease of tissue DA content caused by salsolinol. Neither this increase of prolactin secretion nor the decrease of DA level in spleen could be demonstrated in NE transporter (NET) knock out mice. The results presented argue for the possible role of peripheral norepinephrine release as a target for salsolinol in its action releasing prolactin. The dominant role of norepinephrine transporter may be suggested.     

Evidence for increased hepatic sympathetic nerve activity resulting in hyperglycemia in response to hemorrhage-induced reflex stimulation in anesthetized dogs

To investigate the role of the sympathoadrenal system in glucose mobilization by the liver during hemorrhage, catecholamine (CA) output from both adrenal glands was determined in anesthetized dogs. Venous blood draining from both adrenal glands was combined in a Y-tube that was connected to an electromagnetic flow probe to measure total adrenal venous blood flow. Plasma concentrations of norepinephrine (NE), epinephrine (E), dopamine (DA), and glucose (GL) were determined in various vascular regions. Adrenal CA output (nanograms per minute) under basal conditions was 50.2 +/- 13.6, 181.4 +/- 41.9, and 13.7 +/- 4.8 for NE, E, and DA, respectively. These values were found to increase significantly (P less than 0.05) in response to 5 min of hemorrhage, reaching a maximum output (nanograms per minute) of 663.6 +/- 160.6 (NE), 2503.4 +/- 607.8 (E), and 141.7 +/- 43.7 (DA). Aortic CAs (nanograms per millilitre) increased significantly with a predominant increase in E (0.33 +/- 0.08 to 3.75 +/- 1.03, P less than 0.05). In contrast, increases in portal and hepatic venous CAs (nanograms per millilitre) were characterized by a predominant increase in NE (0.30 +/- 0.06 to 0.64 +/- 0.11 and 0.17 +/- 0.02 to 0.31 +/- 0.07, respectively, P less than 0.05). Hepatic venous and aortic GL concentrations also increased significantly during hemorrhage. Among the various correlations between plasma CA and GL concentrations, the strongest correlation was found between hepatic venous NE and hepatic venous GL (r = 0.804, P less than 0.001). Correlation coefficients obtained with aortic NE and E were weaker but significant (r = 0.603 and r = 0.608, respectively, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Contribution of adrenal norepinephrine output to increase aortic norepinephrine during carotid sinus reflex activation in anesthetized dogs

Changes in circulating plasma catecholamine (CA: E, epinephrine; NE, norepinephrine; and DA, dopamine) concentrations in aortic (AO) blood were investigated in relation to variable rates of CA secretion from both adrenal (ADR) glands in response to bilateral carotid artery occlusion (BLCO) in vagotomized dogs anesthetized with sodium pentobarbital. During BLCO (3 min), AO systolic pressure (AP) increased along with significant increases in ADR-CA output, renal venous (RV) CA output, as well as in AO-E and NE concentrations. A ratio of NE:E in ADR venous and AO blood did not exceed 0.42 +/- 0.09 and 1.09 +/- 0.24 upon BLCO, respectively. In contrast, the NE:E ratio in RV blood increased significantly from 5.39 +/- 0.91 to 9.78 +/- 1.31. Following adrenalectomy (ADRX), the increase in AO-NE in response to BLCO was significantly attenuated by approximately 56%, but the increase in RV-NE output was not affected by ADRX. The results show that in vagotomized dogs, NE is co-released with E from the adrenal glands upon BLCO. The data also indicate that the increase in AO-NE concentration was dependent to a similar extent on the simultaneous increases in ADR-NE output and neuronal NE release. We conclude that under conditions where the sympathoadrenal system is activated, circulating plasma NE concentration may be significantly affected by an increase in ADR-NE output. Sympathetic neuronal contributions would, thereby, be overestimated in assessing overall sympathetic nerve activity by measuring circulating NE. NE concentrations in local venous effluent from individual organs may be more reliable estimates of the sympathetic nerve activity.     

Effects of CL 115,347, (+/-)-15-deoxy-16-hydroxy-16-vinyl-PGE2 methyl ester, on cardiovascular responses and plasma catecholamines in pithed stroke-prone spontaneously hypertensive rats during sympathetic stimulation

The effect of CL 115,347, a topically active antihypertensive PGE2 analog, and PGE2 on changes in blood pressure (BP), heart rate (HR) response and plasma epinephrine (E) and norepinephrine (NE) levels induced by stimulation of the sympathetic spinal cord outflow were studied in pithed stroke-prone spontaneously hypertensive rats (SHRSP). Surgical pithing significantly reduced plasma E but not NE levels suggesting that the sympathoadrenal medullary system differentially affects E and NE release. Sympathetic stimulation of the spinal cord of pithed SHRSP increased HR, BP, plasma E and NE levels. Topically applied CL 115,347 (0.001-0.2 mg/kg) dose-dependently decreased BP, while intravenously infused PGE2 (30 micrograms/kg/min) did not alter BP except for a brief initial drop. Topical application of CL 115,347 (0.1 mg/kg) also inhibited BP responses to sympathetic stimulation without effects on HR or plasma E or NE levels. Intravenous infusion of PGE2 (30 micrograms/kg/min) inhibited both BP and HR responses to spinal cord stimulation but did not alter plasma catecholamine levels. These studies in SHRSP suggest that CL 115,347 and PGE2 modulate cardiovascular responses mainly via postjunctional effects, but act differently on the cardiovascular elements, viz. CL 115,347 acts primarily on blood vessels while PGE2 acts on blood vessels and heart.     

Catecholamines in head and body blood of eels and rats

1. When compared with other vertebrates, the circulating titers of norepinephrine and epinephrine of the yellow eel are very low. 2. The ratio of the catecholamine titers in the eel differs from that reported for other vertebrates. 3. Following decapitation, the titers of the catecholamines are higher in head blood than in body blood of both unanesthetized and anesthetized eels. In decapitated rats, only the dopamine titer is higher in head blood. 4. As in the lamprey, agitation stress causes a drop of circulating catecholamines. However, other forms of stress cause the expected increase. 5. It appears that many data on catecholamines in both brain and circulation of vertebrates in general have been influenced by stress effects.     

Vasoactivity of the ventral aorta of the American eel (Anguilla rostrata), Atlantic hagfish ( Myxine glutinosa), and sea lamprey (Petromyzon marinus)

To determine if vascular smooth muscle from teleost and agnathan fishes expresses receptors for signaling agents that are important in vascular tension in other vertebrates, we exposed rings of aortic vascular smooth muscle from the eel (Anguilla rostrata), the hagfish (Myxine glutinosa), and the lamprey (Petromyzon marinus) to a suite of putative agonists, including: acetylcholine, endothelin, nitric oxide, natriuretic peptides, and prostanoids. Acetylcholine constricted aortic rings from the eel, but had no effect on the rings from lamprey. On the other hand, endothelin constricted rings from all three species. Use of receptor-specific ET agonists demonstrated that only ET(A) receptors are expressed in the eel and lamprey aorta. The nitric oxide donor sodium nitroprusside or nitric oxide itself dilated rings from the eel, but both agonists constricted rings from the hagfish and NO produced a biphasic response (constriction followed by dilation) in the lamprey. Two natriuretic peptides, eel ANP and porcine CNP, produced marginally significant dilation in the eel aorta, human ANP dilated the hagfish rings, and pCNP and eANP dilated the lamprey rings. The prostanoids PGE(1) and PGE(2) both dilated the eel aortic rings, and PGE(1) and carbaprostacyclin (stable PGI(2) agonist) dilated the hagfish and lamprey rings. Our results suggest that receptors for a variety of vasoactive signaling agents are expressed in the aortic smooth muscle of the earliest vertebrates (lamprey and hagfish), as well as the more advanced teleosts (eel).     

Serotonin and MSH secretion: Effect of Parachlorophenylalanine on the pituitary cytology of the eel

Summary Parachlorophenylalanine (pCPA), an inhibitor of tryptophan hydroxylase which depletes brain serotonin in higher vertebrates, was injected into freshwater eels. After 4 or 6 injections (200 mg/kg/day) or 10 injections (100 and 140 mg/kg/day), the animals are paler, with a low melanophore index. In the pituitary gland, granules tend to accumulate in the basal part of the MSH cells and in the perinuclear area. Cells appear smaller with a decreased nuclear area (P< 0.001). In the neurohypophysis, the amount of neurosecretory material is often reduced. Conversely, injections of 5-hydroxytryptophan induce a strong darkening, a result similar to that previously reported in some amphibian species and in one lacertilian species. These data substantiate the hypothesis of a stimulatory influence of 5-hydroxytryptamine on MSH release and possibly its synthesis in the eel and other lower vertebrates.     

INJECTION OF 6-HYDROXYDOPAMINE AND HYDROGEN PEROXIDE INTO THE SUBSTANTIA NIGRA AND LATERAL VENTRICLE OF THE CAT: SPECIFIC AND NONSPECIFIC EFFECTS ON STRIATAL BIOGENIC AMINES1

Attempting to clarify the mechanism by which intracerabral injection of 6-hydroxydopamine (60HDA) reduces catecholamines in the caudate nucleus (CN), we have tested two hypotheses: (1) 60HDA specifically attacks catecholaminergic neurons; (2) 60HDA liberates hydrogen peroxide (H₂O₂) which destroys neurons indiscriminately. To this end, we have injected high or low doses of 60HDA or equimolar amounts of H₂O₂ stereotaxically into the substantia nigra (SN) or the lateral ventricle of cats and have placed electrocoagulative lesions in the SN. We determined the CN levels of dopamine (DA), norepinephrine (NE) and serotonin (5HT) 7-10 days later. Nigral injections of high doses (8 μ mol) of either agent or low doses (80 nmol) of 60HDA decreased both DA and NE and induced similar histologic damage in the SN with neuronal drop-out at the periphery of the lesions. Injection of 80 nmol of H₂O₂ into the SN did not decrease CN amine levels and did not produce histologic damage in the SN. Electrocoagulation of the SN decreased CN DA and NE, but the histologic lesions failed to show any peripheral neuronal drop-out. Ventricular injections of high doses (16 μmol) of 60HDA or H₂O₂ reduced not only DA and NE but also 5HT levels in the ipsilateral CN. Low intraventricular doses (0-16 μmol) of 60HDA decreased only DA and NE without affecting 5HT levels in the CN whereas 0.16 μmol of H₂O₂ had no effect on any of the CN amines. The catecholamine-depleting effects of low doses (80 nmol) of 60HDA were significantly potentiated by inhibiting brain monoamine oxidase by 90 percent or more at the time and site of injection of 60HDA. These results suggest that the extracellular liberation of H₂O₂ from 60HDA could explain some possibly nonspecific effects of high doses of 60HDA; at lower doses, however, 60HDA may act via selective uptake into catecholaminergic neurons with subsequent intracellular release of H₂O₂.     

Effect of mouse epidermal growth factor on plasma concentrations of LH, FSH and testosterone in rams

Two experiments were conducted to examine the effects of mouse epidermal growth factor (EGF) on the concentrations of testosterone, LH and FSH in jugular blood plasma and on the pituitary responsiveness to LHRH. In 20 rams treated with subcutaneous doses of EGF at rates of 85, 98 or 113 micrograms/kg fleece-free body weight, mean plasma LH and testosterone concentrations were significantly reduced (P less than 0.05) at 6 h after treatment but not at 24 h. EGF treatment at 130 micrograms/kg fleece-free body weight suppressed the plasma content of these hormones for up to 48 h. Mean plasma FSH concentrations decreased significantly (P less than 0.05) for up to 48 h after EGF treatment, the effect being most pronounced in rams with mean pretreatment FSH values greater than or equal to 0.5 ng/ml. Intravenous injections of 1.0 micrograms LHRH given to each of 5 rams before and at 6 h, 24 h and 72 h after EGF treatment produced LH and testosterone release patterns which paralleled those obtained in 5 control rams similarly treated with LHRH. These results suggest that, in rams, depilatory doses of mouse EGF temporarily impair gonadotrophin and androgen secretion by inhibiting LHRH release from the hypothalamus. Such treatment appears to have no effect on the responsiveness of the pituitary to LHRH.     

A microdialysis study of the effects of the nicotinic agonist RJR-2403 on cortical release of acetylcholine and biogenic amines

Transcortical dialysis was employed to investigate the effects of subcutaneous (s.c.) injections of RJR-2403 (1.2–7.2 μmol/kg) on extracellular levels of acetylcholine (ACh), norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in rat. Systemic administration of RJR-2403 produced a 90% increase of cortical extracellular ACh levels that persisted for up to 90 minutes after injection. Norepinephrine and DA release were increased 124% and 131% above basal values, respectively. Serotonin (5-HT) levels in the dialysate were also significantly elevated by RJR-2403 (3.6 μmol/kg, s.c.) 70% above baseline at 90 minutes post-injection. Comparison of these responses to those of (−)nicotine from a previous study reveals little difference between the two compounds in their ability to influence cortical neurotransmitter release following systemic administration.     

Capsaicin, a pungent principle of hot red pepper, evokes catecholamine secretion from the adrenal medulla of anesthetized rats

Using a direct monitoring system for catecholamine (CA) secretion into the adrenal vein, we have demonstrated that capsaicin (CAP) evokes CA secretion from the adrenal medulla of pentobarbital-anesthetized rats. A significant increase in epinephrine (E) secretion was seen in rats infused with CAP (200 micrograms/kg, i.v.) without a detectable lag after the infusion. Norepinephrine (NE) secretion evoked by CAP was fairly weak compared with E secretion. The secretion of E evoked by CAP was dose-amount dependent. The stimulation of E release by CAP was barely detectable at 20 micrograms/kg, half-maximal at 100 micrograms/kg, and maximal at 600 micrograms/kg. When CAP (200 micrograms/kg) was infused into rats, the weight-ratio of E to NE was significantly higher (47.6) than when acetylcholine (12.5 micrograms/kg) was infused (13.0). These results indicate that CAP can evoke CA secretion from the adrenal medulla of rats.     

Serotonin synthesis inhibition or receptor antagonism reduces pregnancy-induced nocturnal prolactin secretion

During early pregnancy, two surges of prolactin (PRL) designated as nocturnal (N) and diurnal (D) are displayed by the rat. We previously reported the positive influence of serotonin (5-HT) in regulating the D surge. Its role in the N surge remained inconclusive due to the contradictory results obtained with the 5-HT synthesis inhibitor parachlorophenylalanine (PCPA) and 5-HT2 receptor antagonists. This study further characterizes the involvement of 5-HT in regulating the N surge. The effectiveness of different doses of ketanserin (KET), a 5-HT2 receptor antagonist, to reduce plasma PRL levels during the surge was established. Sub-threshold (1 mg/kg BW) or just maximally effective (10 mg/kg BW) doses of KET were administered to rats that had been pre-treated with PCPA (250 mg/kg BW) for 24h. The lower dose of KET was ineffective in reducing the N surge even though less 5-HT was available due to PCPA treatment 24h earlier. The higher dose was effective in blocking the surge. Subsequently, the effect of one compared to two injections of PCPA 24 hours apart on plasma PRL levels and concentrations of 5-HT, dopamine (DA) and their respective metabolites 5-hydroxy-indoleacetic acid (5-HIAA) and dihydroxyphenylacetic acid (DOPAC) in the medial basal hypothalamus (MBH) and the medial dorsal hypothalamus (MDH) was studied. Two injections of PCPA but not one abolished the N PRL surge. Levels of 5-HT and 5-HIAA were significantly (p less than .005) reduced following either one or two injections of PCPA. Nevertheless, there was a greater (50 fold) decrease in 5-HIAA following 2 injections compared to one injection (10 fold), resulting in lower 5-HT turnover as indicated by lower 5-HIAA/5-HT ratios. Levels of DA in the MBH were reduced significantly only following two injections of PCPA, suggesting that the lack of effect of PCPA after one injection on the N surge was not due to a decrease in DA.