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At least 523 records · Page 29Linked to original sources
PubMed1998

Potentiation of D2-dopamine receptor-mediated suppression of zif 268 by non-competitive NMDA receptor antagonists in reserpinized rats.

Striatopallidal output neurons, which coexpress D2-dopamine receptors and NMDA receptors, are logically a potential site of interaction between corticostriatal glutamatergic input and dopaminergic systems. Recent hypotheses about the etiology of schizophrenia have implicated both excitatory amino acid and dopamine systems. The present study was designed to examine, in vivo, the interaction between D2-dopamine receptors and NMDA receptors in the regulation of the expression of the early immediate genes (IEGs), zif 268 and jun B, in striatopallidal neurons. We tested whether coadministration of NMDA antagonists interacted with the actions of the D2 agonist, quinpirole, on IEG expression following dopamine depletion with reserpine. When rats were pretreated with the non-competitive NMDA receptor antagonists, MK 801 (1 mg/kg) or PCP (20 mg/kg), together with quinpirole, the quinpirole reversal of reserpine induction of zif 268 mRNA was potentiated in all regions examined. MK 801 alone had no significant effect on reserpine induction of zif 268 mRNA. Pretreatment with the competitive NMDA receptor antagonist, CPP (5 mg/kg), did not significantly alter the dose response of zif 268 mRNA expression to quinpirole in any region. There was no significant effect of MK 801 on jun B mRNA expression, either on the response to quinpirole or when administered alone with reserpine. Our findings provide evidence of an interaction between the NMDA receptor channel system and the D2-dopamine system on a molecular level in striatopallidal neurons carrying output from the basal ganglia.

Animals↗
PubMed2003

Effects of adrenomedullin on the contraction of gastric arteries during reserpine-induced gastric ulcer.

Adrenomedullin (100 ng/kg, s.c.) prevents reserpine-induced damage of gastric mucosa. In the model of in vitro gastric arteries from reserpine-treated rats, adrenomedullin pre-treatment resulted in a decrease of the vasoconstriction in response to 5-hydroxytryptamine. In contrast, adrenomedullin pre-treatment of rat with intact gastric mucosa did not affect the vasoconstriction to 5-hydroxytryptamine. In the presence of the NOS inhibitor N(G)-nitro-L-arginine, the responsiveness to 5-hydroxytryptamine in gastric arteries from rats treated with reserpine + adrenomedullin was enhanced to the same level of rats treated with reserpine alone. The anti-ulcer effect of adrenomedullin could therefore be related, at least in part, to an increase of blood flow at the gastric mucosa, by a mechanism involving nitric oxide.

Adrenomedullin↗
PubMed2003

Reserpine responsive myoclonus and hyperpyrexia in a patient with Angelman syndrome.

A case of an older patient with the Angelman syndrome due to a deletion at the 15q11-q13 region is presented. The patient demonstrated generalized prolonged myoclonus severe enough to produce temperatures of 41.4 degrees C and CPK elevations to 7281 U/l. This myoclonus was unresponsive to benztropine, clonazepam and worsened with bromocriptine. It resolved with sleep induced by either lorazepam or diphenhydramine and during treatment with reserpine. Once discharged from the hospital and treated with reserpine, there were much less frequent recurrences of the myoclonus that responded well to concomitant treatment with clonazepam. Later attempts to reduce the reserpine resulted in worsening of the myoclonus. Older patients with Angelman syndrome may display a wide variety of neurologic syndromes. This severe myoclonus in this patient worsened with dopamine agonist treatment and initially improved with dopamine depletion therapy while in the long-term responding best to a combination of clonazepam and reserpine.

Adult↗
PubMed1978

An experimental approach to the breast cancer, reserpine problem.

Reserpine was administered intraperitoneally 3 times weekly to inbred female Syrian BIO hamsters of the 15.16 strain previously shown to be susceptible to methylcholanthrene (MC) induction of mammary cancer. Other groups of hamsters received non-carcinogenic doses of MC along with the reserpine administrations, and an additional group received a carcinogenic dose of MC alone. This last group demonstrated that BIO 15.6 females were indeed susceptible to MC mammary cancer induction, since 4 mg of MC administered by stomach tube (a total dose of 200 mg) caused mammary cancer in 52% of the animals. Mammary cancer was not observed in any of the animals given reserpine or reserpine in combination with the non-carcinogenic dose of MC.

Animals↗
PubMed1998

Effect of serotonin on ouabain-sensitive, K+-dependent, p-nitrophenylphosphatase activity in strial marginal cells of normal and reserpinized guinea pigs.

Na+,K+-ATPase activity is abundant on the basolateral infoldings of the strial marginal cells and contributes to the maintenance of the characteristic electrolyte composition of the endolymph. However, the stria vascularis of the cochlea is known not to be innervated. In order to clarify its humoral regulation by serotonin, the K+-p-nitrophenylphosphatase activity of strial marginal cells was investigated with a cerium-based method in normal guinea pigs and in guinea pigs treated with reserpine, 5-hydroxytryptamine or reserpine plus 5-hydroxytryptamine. K+-p-nitrophenylphosphatase activity was almost completely depressed 3-20 days after reserpine administration. Ten days after reserpinization, followed by repeated 5-hydroxytryptamine treatment, the enzyme activity was detectable. These results suggest that 5-hydroxytryptamine increases the phosphatase activity. Thus, the function of the stria vascularis in producing cochlear endolymph may be regulated by 5-hydroxytryptamine.

4-Nitrophenylphosphatase↗
PubMed1997

Enhanced alpha2A-autoreceptor reserve for clonidine induced by reserpine and cholinomimetic agents in the rat vas deferens.

1. The adaptive changes in the functional parameters of the presynaptic alpha2A-adrenoceptors in rat vas deferens were examined after treatments with the monoamine depleter reserpine or with the direct/indirect cholinomimetic agents pilocarpine and neostigmine. 2. For this purpose, we studied the inhibition induced by the alpha2-adrenoceptor agonist clonidine on the twitch contraction of the vas deferens elicited by electrical field stimulation, in animals that had been treated with acute (single dose), short-term (for 4 days) and chronic (for 11 days) regimens of reserpine (0.25 mg kg(-1), s.c., every 48 h), pilocarpine (10 mg kg(-1), i.p., every 12 h) or neostigmine (0.1 mg kg(-1), i.p., every 12 h). The irreversible receptor alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 300 nM) was used to block partially the alpha2A-adrenoceptor-mediated effect of clonidine. 3. In control (untreated) animals, clonidine inhibited concentration-dependently the twitch response of the vas deferens (pEC50 = 8.66) with a maximal effect near 100%. The apparent affinity constant for clonidine was estimated with the nested hyperbolic methodology (pK(A) = 7.10). The analysis of the occupancy-effect relation for clonidine revealed a large receptor reserve at alpha2A-adrenoceptors. 4. Acute, short-term and chronic treatments with reserpine increased the sensitivity of alpha2A-adrenoceptors to clonidine (decreased the EC50) by about 3, 4 and 9 fold, respectively, and also increased the pool of receptor reserve for this agonist (decreased the K(E)) by 4, 10 and 10 fold, respectively. Receptor affinity values were not changed after treatments. 5. Short-term and chronic, but not acute, treatments with pilocarpine and neostigmine increased the sensitivity of alpha2A-adrenoceptors to clonidine (decreased the EC50) by about 3 and 2 fold, respectively, and also increased the pool of receptor reserve for this agonist (decreased the K(E)) by 2 and 3 fold, respectively. Receptor affinity values were not changed after these treatments. 6. These results indicate that an enhancement of the receptor reserve for clonidine might account for the supersensitivity of alpha2A-adrenoceptors induced by reserpine, pilocarpine or neostigmine treatments in the rat vas deferens.

Adrenergic alpha-Agonists↗
PubMed2002

Alpha-1 adrenoceptor up-regulation induced by prazosin but not KMD-3213 or reserpine in rats.

1. We have investigated the effects of chronic administration of prazosin (a subtype-nonspecific alpha-1 AR antagonist), KMD-3213 (an alpha-1A AR subtype-specific antagonist) and reserpine (a catecholamine depletor) on the density of alpha-1 AR subtypes in various rat tissues (liver, kidney, submaxillary gland, heart and spleen). 2. Administration of prazosin (2 mg kg(-1) day(-1), i.p.) for 2 weeks did not affect K(D) values for [(3)H]-prazosin or [(3)H]-KMD-3213 of alpha-1 ARs in five rat tissues tested. However, it caused 52% up-regulation of alpha-1B AR in the spleen, and 84% and 107% up-regulation of alpha-1A- and alpha-1B ARs, respectively, in the heart. Although major subtypes of alpha-1 AR are alpha-1A AR in the submaxillary gland, alpha-1B AR in the liver, and alpha-1A and alpha-1B ARs in the kidney, these tissues showed no up-regulation. The mRNA levels of alpha-1 AR subtypes were not affected by prazosin administration in any tissue tested. 3. Neither administration of KMD-3213 (2 mg kg(-1) day(-1), i.p.) nor reserpine (0.5 - 1 mg kg(-1) day(-1), i.p.) for 2 weeks caused any change in either the binding affinity for [(3)H]-prazosin or [(3)H]-KMD-3213 or the density of the alpha-1 AR subtypes in the five rat tissues. 4. Neither prazosin nor KMD-3213 treatment reduced the noradrenaline content in the five rat tissues, in contrast to reserpine treatment, which markedly reduced it. 5. The findings of the present study demonstrated that up-regulation of alpha-1 AR is selectively caused by prazosin treatment in some tissues but neither by KMD-3213 treatment nor by chemical denervation with reserpine. These results suggest that up-regulation of alpha-1 ARs is not caused by a simple blockade of sympathetic tone.

Adrenergic Uptake Inhibitors↗
PubMed1996

Processing of chromogranins in chromaffin cell culture: effects of reserpine and alpha-methyl-p-tyrosine.

Bovine chromaffin cell cultures were treated with either reserpine or alpha-methyl-p-tyrosine for up to 10 days. Afterwards the cells were harvested and the degree of proteolytic processing of secretogranin II, chromogranin A and chromogranin B was determined by immunoblotting and HPLC followed by RIA. There was a significant increase in the proteolysis of all three chromogranins after 4-6 days in the presence of reserpine. The small peptides formed in the presence of reserpine in vitro are also produced in vivo. A similar effect was observed with alpha-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase, but the response took up to 10 days to develop. Both drugs decreased catecholamine levels but reserpine was more effective, reaching a high degree of depletion after 4 days. In addition, experiments in vitro indicate that low millimolar amounts of either adrenaline (IC50 5.2 mM) or noradrenaline (IC50 2.4 mM) can significantly impair the proteolytic activity of recombinant murine prohormone convertase 1 when assayed with synthetic fluorogenic and/or peptidyl substrates. We conclude that a lowering of catecholamine levels in chromaffin granules leads to a concomitant increase in proteolytic processing of all secretory peptides. Apparently within chromaffin granules the endoproteases are inhibited by catecholamines and thus their removal leads to increased proteolysis.

Adrenal Medulla↗
PubMed1991

Mechanism of reserpine-induced acute gastric mucosal injury in the rat: role of endogenous 5-hydroxytryptamine.

1. Reserpine (5 mg/kg intraperitoneally) produced gastric mucosal vasoconstriction and injury in all rats within 6 h (injury score 38.8 +/- 2.1 mm2, mean +/- SEM). Coeliac ganglionectomy or the beta-adrenoceptor-blocking drug propranolol (5-15 mg/kg) did not influence these effects of reserpine, but vagotomy protected the rats against them. The alpha-adrenoceptor-blocking drugs phenoxybenzamine and phentolamine at 5 mg/kg were protective against injury. However, a 10 mg/kg dose of either blocker was more effective (2.2 +/- 0.5 mm2 and 3 +/- 0.8 mm2, respectively, versus 38.8 +/- 2.1 mm2, mean +/- SEM, P less than 0.01) and a dose of 15 mg/kg afforded complete protection. 2. Methysergide, a 5-hydroxytryptamine receptor antagonist, produced a dose-dependent increase in the reserpine-induced injury; a significant (P less than 0.05) increase was noted with 15 and 20 mg/kg (47.5 +/- 2.9 mm2 and 49.4 +/- 2.2 mm2, respectively, versus 38.8 +/- 2.1 mm2, mean +/- SEM). 3. The results suggest that, in the rat, reserpine causes vagal alpha-adrenoceptor stimulation producing gastric mucosal vasoconstriction and injury. 5-Hydroxytryptamine is not implicated in the mechanism of this injury and affords protection against it.

Animals↗
PubMed1989

Essential features of the P-glycoprotein pharmacophore as defined by a series of reserpine analogs that modulate multidrug resistance.

We have shown previously that reserpine is an effective "modulator" of P-glycoprotein-associated multidrug resistance (MDR). In addition to enhancing drug cytotoxicity in our multidrug-resistant human leukemia cell line, CEM/VLB100, reserpine strongly competes with a photoactivatible analog of vinblastine, N-(p-azido-3-[125I]iodosalicyl)-N'-(beta-aminoethyl)vindesine, for binding to P-glycoprotein. We also demonstrated previously that there are three substructural domains present in many compounds that modulate P-glycoprotein-associated MDR: a basic nitrogen atom and two planar aromatic rings. In the present study, we wished to test more rigorously the hypothesis that not only are these domains necessary for modulators of MDR but also they must exist in an appropriate conformation. Reserpine is a modulator of MDR in which these domains are present in a well-defined conformation. Accordingly, we prepared eight compounds that vary the spatial orientation of these domains, using either naturally occurring reserpine or yohimbine as chemical templates. When tested for their ability to enhance the cytotoxic activity of natural product antitumor drugs in CEM/VLB100 cells, five compounds that retained the pendant benzoyl function in an appropriate spatial orientation all modulated MDR. By contrast, compounds lacking this moiety failed to do so. These active modulators competed strongly with the 125I-labeled vinblastine analog for binding to P-glycoprotein in plasma membrane vesicles prepared from these cells. Conformational analysis using molecular mechanics revealed the structural similarities of the active modulators. Our results support the hypothesis that the relative disposition of aromatic rings and basic nitrogen atom is important for modulators of P-glycoprotein-associated MDR, and they suggest a ligand-receptor relationship for these agents. These results also provide direction for the definition of an MDR "pharmacophore."

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Effect of norepinephrine on ouabain-sensitive, K+-dependent p-nitrophenylphosphatase activity in strial marginal cells of the cochlea in normal and reserpinized guinea pigs.

On the basolateral infoldings of the strial marginal cells in the cochlea, Na K ATPase activity is abundant. To clarify the humoral control by norepinephrine, K-NPPase activity of strial marginal cells in the cochlea was investigated in normal, reserpine, norepinephrine (NE), reserpine plus NE-treated guinea pigs using a cerium-based method. K-NPPase activity was almost completely decreased 3-20 days after reserpine administration. At 10 days after reserpinization and following NE repeated treatment, enzyme activity was detectable. These results suggested that norepinephrine might restore and regulate strial K-NPPase activity.

4-Nitrophenylphosphatase↗
PubMed1975

Effect of low dose intra-arterial reserpine on vascular wall norepinephrine content.

A number of reports in recent years have indicated that the administration of low dose intra-arterial reserpine has resulted in significant clinical improvement in patients with symptomatic vasospasm, with the benefits presumably resulting from regional vascular wall norepinephrine depletion with resultant vasodilatation. However, to date, there has been no evidence that such low dose reserpine actually alters vascular wall norepinephrine content. This study was performed to determine both regional and systemic effects of low dose intra-arterial reserpine on vascular-wall norepinephrine content, and the duration of any alterations. Twenty-four mongrel dogs had vascular segments excised and assayed for norepinephrine content, before and for up to 4 weeks following a single injection of reserpine, 0.01 mgm/kg, into one femoral artery. The results indicate a pronounced norepinephrine depletion in the injected femoral arterial system, with the reduction persisting for 2-4 weeks, at which time complete norepinephrine recovery occurred. The visceral vessels sampled also showed considerable norepinephrine depletion, indicating systemic spill-over of the drug from the injected peripheral arterial tree. The visceral vessels, however, showed maximal depletion at 24 hours, with recovery by 7 days.

Animals↗
PubMed1979

Effects of reserpine upon thermal stress-induced cardiovascular changes.

The cardiovascular changes induced by 15% total body surface area third-degree burn have been studied in anesthetized dogs. The responses observed were a decrease in plasma volume, a decrease in cardiac output, and a slight but insignificant fall in mean arterial pressure. Graded doses of reserpine ranging from 0.1 to 1.0 mg/kg were administered preceding thermal trauma, and produced a reduction in plasma volume loss. The most effective dose of reserpine was 0.2 mg/kg. Despite the significant reduction (approximately 50%) of plasma volume loss in this dosage group, there were no significant alterations in either cardiac output or mean arterial pressure. These results demonstrate that reserpine is effective in reducing plasma volume loss but ineffective in altering the other cardiovascular parameters observed. Based upon the size of the maximally effective dose in reducing plasma volume loss and the failure of this dose to alter the other cardiovascular responses, it is postulated that the plasma loss reduction may be due to some action of reserpine other than its release of catecholamines and reduction in catecholamine stores.

Animals↗
PubMed2005

Antagonistic interaction between adenosine A2A and dopamine D2 receptors modulates the social recognition memory in reserpine-treated rats.

Increasing evidence suggests that antagonistic interactions between specific subtypes of adenosine and dopamine receptors in the basal ganglia are involved in the control of motor activity. However, there are few studies investigating this interaction in other brain regions and its role in additional functions. In the present study, we evaluated whether reserpine-treated rats (1.0 mg/kg, i.p.) exhibit altered social recognition memory abilities. The effects of acute administration of the dopamine receptor agonists 7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3 benzazepine (SKF 38393, dopamine D(1) receptor agonist) and quinpirole (dopamine D(2) receptor agonist), together with the adenosine receptor antagonists caffeine (non-selective), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, adenosine A(1) receptor antagonist) and 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM241385, adenosine A(2A) receptor antagonist), were also investigated. Twenty-four hours after treatment, reserpine-treated rats exhibited a significant disruption in the ability to recognize a juvenile rat after a short period of time. These animals did not show any motor deficit. The social recognition disruption induced by reserpine was reversed by acute treatment with quinpirole (0.05-0.1 mg/kg, i.p.), caffeine (10.0-30.0 mg/kg, i.p.) or ZM241385 (0.5-1.0 mg/kg, i.p.), but not with SKF 38393 (0.5-3.0 mg/kg, i.p.) or DPCPX (0.5-3.0 mg/kg, i.p.). Moreover, a synergistic response was observed following the co-administration of 'non-effective' doses of ZM241385 (0.1 mg/kg, i.p.) and quinpirole (0.01 mg/kg, i.p.). These results reinforce and extend the notion of antagonistic interactions between adenosine and dopamine receptors, and demonstrate, for the first time, that the blockade of adenosine A(2A) receptors and the activation of dopamine D(2) receptors can reverse the social recognition deficits induced by reserpine in rats.

Adenosine A2 Receptor Agonists↗
PubMed2005

A medication screening trial evaluation of reserpine, gabapentin and lamotrigine pharmacotherapy of cocaine dependence.

AIMS: To conduct a preliminary evaluation of the safety and efficacy of reserpine, gabapentin or lamotrigine versus an unmatched placebo control as a treatment for cocaine dependence. DESIGN: A 10-week out-patient study using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design. SETTING: The study was conducted at the Cincinnati Medication Development Research Unit (MDRU). PARTICIPANTS: Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty participants were enrolled, with 50 participants completing the final study measures. INTERVENTION: The targeted daily doses of medication were reserpine 0.5 mg, gabapentin 1800 mg and lamotrigine 150 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis. MEASUREMENTS: Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression scale--observer and self-report of cocaine use. Safety measures included adverse events, electrocardiograms (ECGs), vital signs and laboratory tests. FINDINGS: Subjective measures of cocaine dependence indicated significant improvement for all study groups. Urine BE results indicated a significant improvement for the reserpine group (P < 0.05) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures. The medications appeared to be tolerated well. CONCLUSIONS: The present findings suggest that reserpine may be worthy of further study as a cocaine dependence treatment.

Adult↗
PubMed1995

Reserpine-induced sulphomucin production by goblet cells in the jejunum of rats and its significance in the establishment of intestinal helminths.

The present investigation was undertaken to determine whether reserpine-induced increase in the sulphation of the small intestinal goblet cell mucins of rats affects the establishment of intestinal helminths. When Wistar rats were given daily intraperitoneal injections of reserpine for seven days and were then implanted intraduodenally with 500 Strongyloides venezuelensis adult worms, the number of adult worms established in the intestine of reserpine-treated rats was about half of that established in controls. Furthermore, when mast cell-deficient Ws/Ws rats were treated with reserpine and implanted concurrently with S. venezuelensis and Nippostrongylus brasiliensis adult worms, the establishment of the former, but not the latter, was significantly suppressed. These results imply that the physicochemical properties of the mucins produced and secreted by the small intestinal goblet cells may be critical for the establishment of particular species of intestinal helminths.

Animals↗
PubMed1991

Effect of reserpine on catecholamine contents and met-enkephalin and beta-endorphin levels in the hypothalamus and the pituitary.

1. The effects of reserpine treatment on the contents of catecholamines and opioid peptides have been studied in the rat hypothalamus and pituitary. 2. Hypothalamic and pituitary catecholamines were drastically depleted following acute reserpine treatment. 3. Reserpine treatment also resulted in a significant decrease in immunoactive met-enkephalin content in both the hypothalamus (25%) and the anterior lobe (50%), but not in the neurointermediate lobe of the pituitary. 4. No changes were observed in immunoactive beta-endorphin levels. 5. These findings suggest that the met-enkephalin contents in the hypothalamus and the anterior pituitary may be under catecholaminergic control. 6. The lack of effect of acute reserpine treatment on immunoactive beta-endorphin contents might be due to the opposing effects of adrenergic and dopaminergic mechanisms.

Animals↗
PubMed1986

Metorphamide levels in chromaffin cells increase after treatment with reserpine.

Exposure of bovine chromaffin cells in primary culture to 0.01-1 microM reserpine caused a dose- and time-dependent increase in intracellular levels of the amidated enkephalin peptide metorphamide. Maximal levels (approximately 800% of control) were obtained at 0.1 microM reserpine and increased levels were apparent by 16 h of treatment. Metorphamide increases were at least fivefold more than that of either Met- or Leu-enkephalin, suggesting that reserpine stimulates both enkephalin processing and amidation in the secretory vesicle. Treatment with elevated potassium, which increases enkephalin levels by stimulating production of preproenkephalin messenger RNA, elicited an increase in metorphamide levels equivalent to, but not greater than, the increase in Met-enkephalin pentapeptide. The ratio of Met-enkephalin to metorphamide in untreated chromaffin cells is approximately 140:1, whereas the final Met-enkephalin: metorphamide ratio in reserpinized chromaffin cells is approximately 30:1, similar to the Met-enkephalin:metorphamide ratio in enkephalinergic neurons of the CNS.

Adrenal Glands↗