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PubMed1980

Responsiveness to vasoactive agents of cerebral and mesenteric arteries isolated from control and reserpine-treated dogs.

1 Pretreatment of dogs for 20 to 24 h before the start of experiments with reserpine (0.5 mg/kg) depleted noradrenaline from cerebral and mesenteric arteries, the diminution being greater in the latter arteries. 2 Contractile responses of helically-cut strips of cerebral and mesenteric arteries to noradrenaline were unaffected by pretreatment with reserpine. Tyramine-induced contractions of mesenteric arteries were markedly attenuated by reserpine-pretreatment, whereas the contraction of cerebral arteries was not influenced. The contractile response of mesenteric arteries to transmural nerve stimulation or nicotine was abolished by reserpine-pretreatment, but the relaxation induced by nicotine of cerebral arteries contracted with prostaglandin F2 alpha was not affected. Pretreatment with reserpine attenuated the contractions of mesenteric arteries induced by angiotensin II, but did not alter the response of cerebral arteries to 5-hydroxytryptamine. 3 In prostaglandin-contracted cerebral and mesenteric arterial strips, relaxant effects of acetylcholine, isoprenaline and K+ were not significantly influenced by reserpine-pretreatment. 4 It appears that tyramine and nicotine do not release noradrenaline from dog cerebral arteries in amounts sufficient to cause significant contractions. Attenuation of the response to angiotensin II by pretreatment with reserpine is not the result of depletion of noradrenaline from the mesenteric arterial wall but may be due to interference with the mechanism specific to actions of angiotensin II.

Acetylcholine↗
PubMed1988

Neuropeptide Y and reserpine-resistant vasoconstriction evoked by sympathetic nerve stimulation in the dog skeletal muscle.

1. The effects of sympathetic nerve stimulation (evoked by recordings of authentic irregular vasoconstrictor nerve fibre discharge with average frequencies of 0.59, 2.0 and 6.9 Hz) on the perfusion pressure and the overflow of noradrenaline (NA) and neuropeptide Y-like immunoreactivity (NPY-LI) were investigated in the blood-perfused gracilis muscle of the dog in situ. 2. Nerve stimulation in the untreated control group evoked a frequency-dependent increase in perfusion pressure and overflow of NA. A significant overflow of NPY-LI was found at the highest frequency only. 3. In a separate group of animals, the sympathetic supply was unilaterally interrupted by preganglionic decentralization before the administration of reserpine (1 mgkg-1 i.v.) 24 h before the experiment. Reserpine reduced the NA content of the intact and decentralized gracilis and gastrocnemius muscle by 98-99%. Reserpine also induced a marked (80%) reduction of the muscular content of NPY-LI. The depletion of NPY-LI was, in contrast to that of NA, prevented by the decentralization, suggesting that nerve impulse activity was of primary importance for the reserpine-induced depletion of NPY-LI. 4. A slowly developing and long-lasting perfusion pressure increase was evoked by nerve stimulation, at 2.0 and 6.9 Hz after reserpine treatment. These responses were larger in the decentralized, as compared to the intact gracilis muscle and correlated with the nerve stimulation evoked overflow of NPY-LI (r = 0.79, P less than 0.001). Stimulation at 0.59 Hz caused vasoconstriction in the decentralized but not in the intact gracilis. 5. Administration of alpha,beta,-methylene adenosine triphosphate did not evoke an increase in perfusion pressure in the gracilis muscle of reserpine-treated animals. 6. In conclusion, a large perfusion pressure increase to sympathetic nerve stimulation occurs in the reserpine-pretreated skeletal muscle vasculature of the dog in vivo, providing that preganglionic decentralization has been performed. It is suggested that the released NPY-LI may mediate this vasoconstrictor response.

Adenosine Triphosphate↗
PubMed1990

Reserpine induces vascular alpha 2-adrenergic supersensitivity and platelet alpha 2-adrenoceptor up-regulation in dog.

1. The aim of the present study was to investigate the influence of catecholamine levels on the regulation of alpha 2-adrenoceptor sensitivity in dogs. 2. Blood pressure and heart rate values at rest, plasma catecholamine levels, platelet and adipocyte alpha 2-adrenoceptors as well as the alpha 2-mediated cardiovascular responses to clonidine (10 micrograms kg-1 i.v., after alpha 1-, beta-adrenoceptor plus muscarinic blockade) or noradrenaline (0.5, 1, 2 and 4 micrograms kg-1 i.v. after alpha 1- and beta-adrenoceptor blockade) were measured before and after reserpine treatment (0.1 mg kg-1 day-1 s.c. over 15 days). 3. Reserpine induced a significant decrease in resting systolic and diastolic blood pressures (213 +/- 2/87 +/- 6 mmHg before vs 158 +/- 5/59 +/- 3 mmHg after treatment) as well as in heart rate (91 +/- 2 beats min-1 before vs 76 +/- 3 beats min-1 after treatment). 4. A 5 min tilt test performed under chloralose anesthesia, failed to modify blood pressure before treatment whereas it induced a significant fall in the same animals after the 15 day treatment. Plasma levels of noradrenaline significantly decreased (262 +/- 58 vs 66 +/- 31 pg ml-1) whereas plasma adrenaline levels were unchanged. 5. The alpha 2-mediated pressor responses to noradrenaline were significantly increased after reserpine. Clonidine induced a marked pressor effect (+72 and +45% in systolic and diastolic blood pressures respectively) after reserpine treatment. This effect was suppressed by administration of RX-821002, a new specific alpha 2-adrenoceptor antagonist. 6. Reserpine treatment significantly increased platelet alpha 2-adrenoceptor number (identified with [3H]- yohimbine or [3H]-RX821002) with no change in Kd values. alpha 2-Adrenoceptor number remained unchanged in adipocytes (identified with [3H]-RX821002). 7. These results show that a 15 day treatment with reserpine induces a vascular alpha 2-adrenergic supersensitivity and an up-regulation in platelet alpha 2-adrenoceptors. In contrast, this phenomenon does not involve all the tissues since adipocyte alpha 2-adrenoceptors escape the effect of reserpine. We suggest that the levels of plasma noradrenaline play an important role in the regulation of the platelet and vascular alpha 2-adrenoceptors. In contrast, adipocyte alpha 2-adrenoceptors are not affected by changes in plasma noradrenaline levels.

Adipose Tissue↗
PubMed1985

Modification of reserpine induced rigidity by dopaminergic and alpha-adrenergic drugs.

Previous studies have reported that a variety of drugs are effective in preventing reserpine-induced hypertonus, including dopamine agonists and alpha-adrenergic antagonists. The purpose of this study was to use a quantitative measure of hindlimb muscle tone to evaluate the relative efficacy of various drugs with known pharmacologic actions on dopaminergic and adrenergic receptors. The results show that adrenergic antagonists (yohimbine, thymoxamine, phentolamine, RS 21361) were the most effective in protecting against the effect of reserpine. Along with the dopamine precursor, 1-DOPA, these drugs were not only effective but also they produced no muscle relaxation in non-reserpinized rats. Although dopamine agonists (apomorphine, lisuride, bromocriptine) also protected against reserpine-induced rigidity, these drugs also produced muscle relaxation in non-reserpinized rats. A variety of drugs with alpha adrenergic agonist, beta adrenergic antagonist, dopamine antagonist and antihistamine activity did not alter the reserpine-induced rigidity despite generalized muscle relaxant effects with some of these. The results show that alpha adrenergic antagonists are the most selective agents in preventing reserpine-induced rigidity and suggest that alpha-2 receptors primarily mediate this effect.

Adrenergic alpha-Antagonists↗
PubMed1988

Renal sympathetic nerve activation in relation to reserpine-induced depletion of neuropeptide Y in the kidney of the rat.

The effect of reserpine treatment on renal sympathetic nerve activity and tissue levels of neuropeptide Y (NPY)-like immunoreactivity (LI) and noradrenaline (NA) were studied in rats. Injection of reserpine (1 mg kg-1 i.v.) caused a clear-cut (about 50%) increase in rectified activity of the post-ganglionic sympathetic nerves to the kidney within 15 min in chloralose-anaesthetized rats compared to a saline-treated control group. This increase in nerve activity was still maintained 120 min after the reserpine injection. The renal nerve activation was accompanied by a progressive fall in mean arterial blood pressure and an initial tachycardia. In a separate group of conscious rats, the levels of NPY-LI (1.3 +/- 0.06 pmol g-1) and NA (1.6 +/- 0.07 nmol g-1) in the kidney were significantly reduced (by 74 and 83%, respectively) 24 h after reserpine treatment (1 mg kg-1 i.v.). The reserpine-induced depletion of NPY-LI, but not that of NA, was inhibited by pretreatment with the ganglionic blocking agent chlorisondamine or the alpha 2-adrenoceptor agonist clonidine, both of which are known to decrease renal sympathetic nerve activity. The tissue content of NPY-LI in the right atrium (16.3 +/- 0.7 pmol g-1) was not reduced by reserpine. Arterial plasma NPY-LI in the rat was high (222 +/- 5 pmol l-1), and this value did not change after pretreatment with reserpine, chlorisondamine or clonidine, indicating that, in the rat, circulating NPY-LI is not a good indicator of sympatho-adrenal activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Effect of reserpinization on insulin secretion in the rat.

Reserpine-induced supersensitivity to the insulin-releasing action of a beta-adrenergic agonist, isoprenaline, and of glucose was studied in vivo and in vitro. The subcutaneous injection of rats with reserpine (0.05 to 10 mg kg-1) enhanced the action of isoprenaline on insulin secretion. ED50 of isoprenaline for insulin secretion was changed little after reserpinization, whereas maximum effect of the beta-agonist was enhanced by pretreating rats with reserpine. Glucose-stimulated insulin secretion was also enhanced in the reserpinized rats. Pancreases isolated from the reserpinized rats secreted more insulin in response to phentolamine in the presence of glucose and isoprenaline. These results suggest that the supersensitivity in insulin secretion induced by reserpine may be non-specific.

Animals↗
PubMed1985

Reserpine is a calcium channel antagonist in normal and GH3 rat pituitary cells.

Reserpine exerts direct effects on several tissues, including inhibition of hormone release from rat anterior pituitary cells. To test the hypothesis that reserpine may be acting as a calcium channel antagonist, normal or GH3 rat anterior pituitary cells were preincubated in reserpine or the conventional calcium channel blocker, D-600, followed by exposure to 45Ca2+ together with stimulants of calcium uptake: maitotoxin, a potent calcium channel activator; A23187, a calcium ionophore; or 50 mMK+. After incubation, the cells were harvested by vacuum filtration and cell-associated radioactivity determined. In normal cells, reserpine blocked both basal and K+-stimulated calcium uptake. Reserpine selectively blocked maitotoxin but not A23187-induced calcium uptake. In GH3 cells 9 microM reserpine and 30 microM D-600 were equally effective in blocking maitotoxin-stimulated calcium uptake. Reserpine appears to block voltage-dependent calcium channels in pituitary cells in a concentration-dependent manner but not calcium uptake caused nonspecifically by A23187.

Animals↗
PubMed1997

Cytochemical localization of ouabain-sensitive, K(+)-dependent p-nitrophenylphosphatase activity in the facial nerve of reserpinized guinea pigs.

Ion-transporting Na,K-ATPase plays an essential role in nerve conduction. To clarify the cytochemical effects of reserpine on transport Na,K-ATPase activity, the localization of ouabain-sensitive, K(+)-dependent p-nitrophenylphosphatase (K-NPPase) activity was investigated in the facial nerves of normal and reserpinized guinea pigs using a cerium-based method. In the normal facial nerve, the reaction product of K-NPPase activity was observed on the internodal axolemma and Schmidt-Lanterman incisures. In the Ranvier nodes, enzyme activity was localized to the paranodal and nodal axolemma. In the reserpinized nerves, reaction product was detectable on the nodal axolemma but was undetectable on the other parts of the axolemma. Nodal K-NPPase was not affected by reserpine treatment. Therefore, the transport Na,K-ATPase on the nodal axolemma might differ from that on the other parts of the axolemma. Allowing reserpinized animals to survive. Two different ouabain-sensitive K-NPPase reactivities, "reserpine-sensitive" and "reserpine-resistant," might be present in the facial nerve of guinea pigs.

4-Nitrophenylphosphatase↗
PubMed1989

Alterations of pancreatic growth and of GP-2 content in the reserpinized rat model of cystic fibrosis.

The chronically reserpinized rat is an experimental model for cystic fibrosis. In this study, we report the effects of two doses of reserpine (0.5 and 1.0 mg.kg-1.d-1) on the growth of the pancreas and on its content of the glycoprotein GP-2, a characteristic protein of the zymogen granule. An assessment of the effects of secondary malnutrition induced by the drug was also performed by adding a group of pair-fed animals. During the 7 d of treatment, body wt and food intake were monitored. These two parameters were significantly affected from the 4th d on. Pancreatic wt, DNA, protein, and activity of amylase and chymotrypsinogen were measured after 4 and 7 d of treatment; lipase activity and GP-2 content, after 7 d. Although the DNA content never did change, total protein diminished by 27% at the higher dose of reserpine. Pancreatic wt, amylase activity and GP-2 content were reduced by the treatment, while chymotrypsinogen and lipase activities were increased. Effects on pancreatic wt, amylase, chymotrypsinogen, and GP-2 were dose-dependent. Malnutrition had effects similar to reserpine on body wt, protein, amylase, and chymotrypsinogen. Pancreatic wt, lipase, and GP-2, however, were specifically altered by the chronic reserpine treatment. It is concluded from these results that reserpine induces, in the pancreas, specific alterations that are distinguishable from the accompanying malnutrition. These findings support the use of pancreatic wt, lipase, and GP-2 as specific markers of the effects of the drug on the pancreatic tissue in the chronically reserpinized rat model for cystic fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1975

Treatment of Cushing's disease with reserpine and pituitary irradiation.

Eighteen patients with Cushing's disease were treated with reserpine and pituitary irradiation. Complete remission was obtained in 9 out of 18 patients after reserpine treatment of 1-2 mg per day for a mean period of 20.4 months, and pituitary irradiation with a mean of 5,865 rads. In another 9 patients, reserpine 0.8-2 mg per day for a mean period of 22.5 months, and pituitary irradiation with a mean of 6,650 rads, were employed. Of these 9 patients, an additional subtotal adrenalectomy was carried out in 6 patients who are now in complete remission. Because of severe psychic symptoms resulted from the original disease in 2 of the remaining 3 patients, subtotal adrenalectomy was performed first and pituitary irradiation and reserpine treatment followed. Remission was eventually obtained in these 2 cases. One patient refused the operation, and thus had little clinical remission. All of the 17 cases in remission were followed up for periods of 6 months to 10 yr. During this time, only one case which had responded to reserpine and pituitary irradiation relapsed, but regained remission following resumption of therapy. Another died of cerebral glioblastoma 4 yr after remission of the disease. It was noteworthy that endocrinologic data including: plasma levels of ACTH and 11-OHCS, suppressibility by dexamethasone, responses of plasma GH to arginine and to insulin loads, and diurnal rhythm of plasma 11-OHCS were nearly normal in a considerable number of the cases in remission. Effectiveness of the combined therapy with reserpine and pituitary irradiation for treating Cushing's disease may support a working hypothesis that reserpine acts through some as yet unknown mechanism to correct a presumed central nervous disorder, while suitable pituitary irradiation probably corrects the pituitary dysfunction directly.

Adrenalectomy↗
PubMed1975

[Central action of beta-phenylethylamine derivatives. (4) Effects on spontaneous motor activity and body temperature of beta phenylethyamine derivatives injected into the brain in reserpine pretreated mice].

Effects on spontaneous motor activity and body temperature of beta-phenylethlamine derivatives injected into the cerebral ventricles in reserpine or reserpine and isocarboxazide pretreated mice were investigated with the following results. 1) Each injection of tyramine (40 mug) and dopamine (40 mug) increased the spontaneous motor activity measured by the photo-cell counters method in reserpinized mice. 2) Each injection of tyramine (40 mug), dopamine (40 mug) and beta-phenylethylamine (40 mug) increased the spontaneous motor activity measured by both the wheel cage and photo-cell counters methods in reserpine and isocarboxazide-pretreated mice, but noradrenaline (20 mug) and isoproterenol (80 mug) did not increase the spontaneous motor activity as determined by both methods. 3) The injection of tyramine (40 and 80 mug), dopamine (10 and 40 mug) and p-octopamine (40 mug) increased the body temperature in reserpine and isocarboxazide pretreated mice. 4) Tyramine, dopamine and p-octopamine caused a marked increase in the body temperature as compared with control injection in reserpine and isocarboxazide-pretreated mice, whereas isoproterenol had no influence on body temperature. Our results suggest that beta-phenylethylamine derivatives have different effects in reserpinized and non-pretreated states.

Animals↗
PubMedDate not supplied

The effect of reserpine on acetylcholine synthesis, choline acetylase and cholinesterase activity.

The effect of reserpine on acetylcholine synthesis, choline acetylase and cholinesterase activity. Acta Physiol. Pol. 1975, 26 (1): 55-61. Reserpine-induced changes in ACh content in various tissues of white rats (cerebral cortex and brain stem, stomach, lungs, heart, spleen) and the effects of reserpine on the synthesis, enzymatic breakdown of ACh, and ChAc activity were studied. Reserpine administered subcutaneously caused a singificant rise in ACh content of the cerebral cortex and insignificant rise in the heart and spleen. Reserpine (in a concentration of 0.25 mug/ml) had no effect on ACh synthesis in vitro. Reserpine in vivo increased significantly ACh synthesis in the brain. No effect of reserpine on ChAc and AChE activity was demonstrated.

Acetylcholine↗
PubMed1975

Renal hemodynamics and electrolyte excretions after reserpine and ethanol.

The participation of the peripheral nervous system in the renal response to an acute ethanol administration was investigated in dogs. The animals received water or ethanol (3 g/kg), with and without 2 days pretreatment with reserpine. Each group was examined 18 hours after the water or ethanol administration. In comparison to water controls, both reserpine and ethanol produced similar increases with respect to renal hemodynamics. The combined treatment produced a further significant increase in effective renal plasma flow. Reserpine alone produced increases in the rates of filtration and reabsorption of sodium and chloride; ethanol and reserpine-ethanol treatments produced further increases but did not alter the excretory rates. Although all three treatments produced increases in the rate of filtration of potassium, only ethanol and reserpine-ethanol treatments increased the excretory rate. Magnesium excretion was decreased by reserpine and reserpine-ethanol in comparison to water and ethanol, respectively; but calcium excretion was elevated in all the treatment groups. Zinc excretion was increased in the ethanol group. The results suggest that the secondary action of ethanol to produce release and possible depletion of peripheral catecholamine stores is not primarily involved with its renal effects, except in the case of magnesium and zinc metabolism.

Animals↗
PubMed1992

Role of 5-hydroxytryptamine (5-HT) in the mechanism of reserpine-induced stimulation of H+ output in the rat. A new hypothesis for the mechanism of gastric acid secretion.

This study was undertaken in the rat to examine the role of 5-hydroxytryptamine (5-HT) in the mechanism of reserpine (0.1 mg/kg)-induced stimulation of gastric acid secretion. Reserpine significantly (p < 0.001) stimulated acid secretion relative to control values (197 +/- 3.1 vs 61 +/- 1.7 mumol, mean +/- SEM, n = 10). Atropine (5 mg/kg) and cimetidine (40 mg/kg) were equally effective in achieving a significant (p < 0.001) suppression of the reserpine-induced acid secretion (98 +/- 3.4 and 91 +/- 2.9 mumol, respectively, vs 197 +/- 3.1 mumol, mean +/- SEM, n = 10), an action intensified by administering them together, but not significantly so (84 +/- 5.3 mumol). Vagotomy was more effective (p < 0.001) than the latter combination in preventing acid stimulation by reserpine and allowed an acid output similar to that of vagotomy controls (14 +/- 1.2 vs 13 +/- 1.4 mumol, mean +/- SEM, n = 10). Dose dependent inhibition of the reserpine-induced stimulation of acid secretion was achieved by the 5-HT receptor antagonist methysergide, an inhibition significantly (p < 0.001) more effective than that afforded by vagotomy coupled with achlorhydria in 80% of animals was noted with the 5-20 mg/kg doses. Reserpine produces vagal adrenergic delivery to the stomach, which releases acid secretagogues and sensitizes parietal cells to them besides stimulating acid secretion, and 5-HT is discharged into the gastric mucosa by vagal adrenergic activity and by reserpine and liberates acid secretagogues by a paracrine action.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

[Reserpine-induced supersensitivity and alpha 1-adrenoceptor subtypes].

Supersensitivity is one of classical and pharmacological phenomena, and may be caused by a variety of procedures, including surgical and chemical denervation and chronic treatment with antagonists. We examined reserpine-induced chemical denervation supersensitivity with special reference to arterial alpha 1-adrenoceptor (alpha 1-AR) subtypes. Chronic treatment with reserpine for 2 weeks produced supersensitivity in the contractile response to phenylephrine of isolated rat tail artery, resulting a leftward shift of concentration-response curve (10 fold shift at EC50 value). This supersensitivity in reserpine-treated artery was selectively inhibited by BMY7378 (alpha 1D-AR selective antagonist) but not by KMD-3213 (alpha 1A-AR selective antagonist). On the other hand, the response to phenylephrine in reserpine-untreated artery was inhibited by KMD-3213 but not by BMY7378. Tissue segment binding study with 3H-prazosin revealed that high affinity binding sites for BMY7378 were detected with a proportion of 32% in reserpine-treated tail artery but absent in untreated artery, although total density of alpha 1-ARs was not changed by reserpine-treatment. The present results strongly suggest that reserpine-induced supersensitivity of rat tail artery is caused by a selective induction of alpha 1D-AR subtype.

Animals↗
PubMed2005

Indirect biochemical evidence that reserpine methiodide produces selective depletion of peripheral biogenic amines in rats.

Reserpine, an alkaloid from Rauwolfia serpentina was widely used for its antihypertensive action in the past. In the present investigation, reserpine methiodide (RMI), a quaternary analogue of reserpine was synthesised and evaluated biochemically for its central and peripheral amine depleting actions in rats and compared with reserpine. The 24 h urinary excretion of vanillylmandelic acid (VMA), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the respective metabolites of noradrenaline, serotonin and dopamine were estimated and considered as indirect biochemical indices for the amine depleting action of reserpine and RMI. The results indicate that RMI at doses of equal to and double the equimolar doses of reserpine was found to deplete the peripheral amines without affecting the central stores of the amines. The results further suggest that the quaternization of reserpine might restrict its transfer across the blood-brain barrier and could be the reason for its selective peripheral action.

Animals↗
PubMed1991

Reserpine-induced supersensitivity in rat caudal artery: influence of age.

Vascular smooth muscle function does not necessarily deteriorate with advancing age. However, although base-line function may be well maintained, the ability to adapt to stress may decline. Therefore we tested the hypothesis that development of denervation supersensitivity may be impaired in older animals. Fischer-344 rats (6, 12, 20, 24 and 27 months old) were treated with reserpine 0.3 or 0.4 mg/kg i.p. for 7 days, a dose which was sufficient to deplete fully vascular norepinephrine content. Isometric contractile responses to phenylephrine and serotonin of isolated tail artery rings were determined. In the oldest animals studied, 27 months, chronic reserpine treatment resulted in depressed tail artery contractile responses, perhaps due to a toxic effect of the reserpine treatment. Reserpine-induced supersensitivity, reflected by a decreased EC50, developed to both agonists at all other ages studied. For serotonin, the degree of reserpine-induced supersensitivity did not change with age. However, for phenylephrine, the shift in the concentration-response curve after reserpine treatment was less in 6-month-old rats as compared to all other ages. There was no change in the development of supersensitivity from 12 to 24 months of age. These findings suggest that the development of reserpine-induced supersensitivity is not impaired in blood vessels of older animals and that the ability to adapt to changing conditions is also maintained with age.

Age Factors↗
PubMed1975

Effects of 6-hydroxydopamine and reserpine on amphetamine-induced release of norepinephrine in rat cerebral cortex.

Amphetamine released 3-H-norepinephrine from rat cerebral cortex tissue which had previously accumulated the 3-H-amine. Destruction of noradrenergic nerve endings by pretreatment of the rats with 6-hydroxydopamine inhibited the accumulation of 3-H-norepinephrine by the tissue and reduced the proportion of the 3-H-amine which was released by amphetamine. Inhibition of storage of 3-H-norepinephrine within nerve endings by pretreatment of the animals with reserpine also reduced accumulation of 3-H-norepinephrine but did not reduce the proportion of the accumulated 3-H-amine which was released by amphetamine. The addition of desipramine (an inhibitor of neuronal uptake) further reduced the accumulation of 3-H-norepinephrine in animals pretreated with reserpine but had no further effect in animals pretreated with 6-hydroxydopamine. A greater proportion of the 3-H-norepinephrine was converted to 3-H-deaminated metabolites in tissues of reserpine-treated animals than in the tissues of control or 6-hydroxydopamine-treated rats. Amphetamine-induced release of 3-H-norepinephrine was partially calcium dependent in tissues from control animals. After reserpine treatment, amphetamine-induced release of norepinephrine was independent of calcium, whereas potassium-mediated release was still markedly calcium dependent. These experiments indicate that amphetamine releases 3-H-norepinephrine primarily from storage sites within central adrenergic nerve endings. An analysis of the time course of release from tissues of rats treated with reserpine suggests that amphetamine is equally capable of releasing 3-H-norepinephrine from granular sites which are susceptible to reserpine and from reserpine-insensitive sites.

Amphetamine↗