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PubMed1990

Reserpine-induced decrease in type I and II corticosteroid receptors in neuronal and lymphoid tissues of adrenalectomized rats.

The effect of the biogenic amine depleting drug, reserpine, on the concentration of type II corticosteroid receptors (i.e., glucocorticoid receptors) in neuronal (hippocampus, frontal cortex, hypothalamus), lymphoid (circulating lymphocytes, spleen, thymus) and pituitary tissues as well as hippocampal type I (i.e., mineralocorticoid) receptors was examined in adrenal-intact and adrenalectomized (ADX) rats. Reserpine (2 mg/kg) or vehicle was administered to adrenal-intact rats for 2 consecutive days. Following the second injection rats were ADX and sacrificed 24 h later. Reserpine significantly decreased type I and II hippocampal receptors as well as type II receptors in frontal cortex, hypothalamus, lymphocytes and spleen. Since the reserpine-induced decreases in receptor content could be due to reserpine-induced elevations in circulating corticosterone levels, reserpine (2 mg/kg) or vehicle was administered to 1-day ADX rats which were then sacrificed 2 days later (i.e., 3 days post ADX). A 1-day ADX control group was also included. The 3-day ADX regimen produced significant or nearly significant increases in type II receptors in hippocampus, frontal cortex, hypothalamus, lymphocytes and spleen in vehicle-treated rats. Reserpine attenuated the ADX-induced upregulation of type II receptors in hippocampus, frontal cortex, lymphocytes and spleen, but had no effect on the ADX-induced upregulation of type II receptors in the hypothalamus. The ADX-induced increase in hippocampal type I receptors was not affected by reserpine treatment. In a final experiment, reserpine (2 mg/kg) or vehicle was administered immediately after ADX and rats were sacrificed 24 h later in order to assess the effect of reserpine on basal (i.e., nonupregulated) corticosteroid receptor levels in the absence of circulating corticosterone levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed1994

Alterations of the pancreatic secretory responses to secretin and to the ionophore A23187 by reserpine: a calcium-mediated phenomenon?

This study was undertaken to further characterize the secretory response of the rat pancreas after reserpine treatment. Rats were given reserpine (1 mg kg-1 day-1 i.p.) or vehicle for 7 days. To distinguish between specific effects of reserpine and those related to secondary malnutrition caused by the drug, the secretory response of a group of pair-fed (PF) animals to reserpine was also investigated. Amylase release from dispersed pancreatic acini, prepared from control (C), PF and reserpine-treated (R) rats were used to evaluate functional secretory capacity. Reserpine and pair-feeding caused reduced responses of pancreatic acini to secretin. The pair-feeding-altered secretin response was greatly improved by increasing extracellular Ca2+ concentration, whereas a slight improvement was noticed in the R group. Reserpine significantly reduced the secretory response to the ionophore A23187 at concentrations above 5 x 10(-7) M in 1.25 mM Ca2+; in 2.5 mM Ca2+, the response to the ionophore was significantly higher in the R group than in C at all ionophore concentrations. Furthermore, at 2 x 10(-7) M ionophore, the secretory response to secretin in the R group became significantly higher than that in the C group but comparable to that of the control+ionophore. In conclusion, reserpine affects the secretory response to secretin as did pre-exposure of pancreatic acini to a high concentration of carbamylcholine. The modified secretory response to the ionophore following reserpine treatment indicates that reserpine may act as a 'Ca2+ entry mechanism' antagonist which may explain the partial reduction in the secretin response.

Amylases↗

PubMed1986

Effects of malnutrition and chronic reserpine treatment on pancreatic exocrine function.

The chronically reserpine-treated rat, an experimental model for cystic fibrosis, exhibits generalized exocrinopathy, impaired pancreatic secretion, and decreased pancreatic amylase. Although chronic reserpine treatment induces malnutrition by decreasing food consumption and growth, the effects of this malnutrition per se on the exocrine pancreas have not been considered. In this study, the effects of chronic reserpine treatment and malnutrition on the exocrine pancreas were determined using pair-fed controls. Male, Sprague-Dawley rats were treated daily subcutaneously for 5 to 7 days with: no injection (control), 1.0 ml/kg vehicle or sham (control-sham, pair fed-sham), or 0.5 mg/kg reserpine (chronically reserpine-treated). Both chronic reserpine-treatment and pair-feeding significantly decreased food consumption (40%), body weight (51 and 59%), total pancreatic amylase (49 and 56%) and specific amylase activity (62 and 61%), pancreatic protein (65 and 75%), and pancreatic weights (62 and 65%) compared to controls. These decreases, however, were comparable between the chronically reserpine-treated and pair fed-sham rats. In contrast, the secretory response to the biologically active cholecystokinin analog cholecystokinin octapeptide was significantly attenuated in isolated pancreatic acini prepared from reserpine-treated rats compared to that from either control or pair-fed sham rats. Malnutrition decreased pancreatic amylase activity and protein comparably to reserpine treatment, but only partially attenuated the secretory response to cholecystokinin octapeptide. Based on the results of this study, pair-fed controls should be used to distinguish between the effects of reserpine alone and the induced malnutrition on pancreatic exocrine function in studies of this experimental model of cystic fibrosis.

Amylases↗

PubMed1988

Effects of reserpine treatment on dietary adaptation of the rat exocrine pancreas.

Chronic reserpine treatment (500 micrograms/kg) of the rat results in generalized exocrinopathy, impaired pancreatic secretion, and decreased pancreatic amylase. These characteristics are similar to those in cystic fibrosis and are the basis for use of this experimental model for cystic fibrosis. Pancreatic enzymes adapt to diet, but it is not known whether chronic reserpine treatment affects this response. Due to the malnutrition induced by this treatment, another dose of reserpine was required that would alter pancreatic function but not induce malnutrition in order to evaluate dietary adaptation. Male rats (100-120 g) were injected subcutaneously daily for 7 days with 1) no injection (control); 2) 1.0 ml/kg vehicle or sham (pair fed-sham); or 3) reserpine: 500, 50, or 5 micrograms/kg. Food consumption was comparable among control and reserpine-treated (50 and 5 micrograms/kg) rats and significantly greater (200%) than pair fed-sham and 500 micrograms/kg reserpine-treated rats. Pancreatic amylase, however, was significantly lower in all reserpine-treated rats (500 micrograms/kg, 74%; 50 micrograms/kg, 56%; 5 micrograms/kg, 52%) than in control rats. To evaluate dietary adaptation, control and reserpine-treated (5 micrograms/kg) rats were fed high carbohydrate, high fat or high protein diets. Both groups adapted to these diets with the greatest amylase, lipase, and trypsin activities in high carbohydrate-, high fat-, and high protein-fed rats, respectively. Reserpine-treated rats fed high carbohydrate, however, had significantly lower (64%) amylase activity than high carbohydrate-fed control rats. Although reserpine-treated rats can adapt pancreatic enzymes to diet, the adaptation of amylase to carbohydrate is impaired.

Amylases↗

PubMed1976

[Findings in the gastric mucosa and gastric secretion in rats treated with methyl O-(4-hydroxy-3-methoxycinnamoyl)reserpate (CD-3400) and reserpine derivatives].

CD-3400 developed by Nippon Chemiphar Co. Ltd., is a new antihypertensive agent belonging to the class of rauwolfa alkaloids. Influence of the agent on gastric mucosa, healing process of acetic acid-induced gastric ulcer and gastric juice in rats was investigated and compared with effects of reserpine and rescinnamine. CD-3400-induced gastric lesions were fewer in number than those produced with reserpine and rescinnamine in fasted rats. After a three day treatment of CD-3400 to fed rats, however, there were few gastric lesions, while reserpine- and rescinnamine-induced gastric lesions were aggravated to a greater extent that when a single administration was given to fasted rats. Influence of CD-3400, reserpine and rescinnamine on the healing process of acetic acid-induced ulcer was insignificant, but treatment with high doses of reserpine and rescinnamine resulted in death. Pretreatment with CD-3400 and reserpine produced a decrease in gastric acid and K+, and an increase in Na+. Repeated administration of reserpine for 5 days resulted in a decrease of both gastric volume and acid, while such was not seen with CD-3400. Treatment with anticholinergic agents such as atropine sulfate and atropine methylbromide inhibited CD-3400- and reserpine-induced gastric lesions. From these results, it would appear that cholinergic factors play a role in the pathogenesis of CD-3400-induced gastric lesions, as in the case with reserpine, and that the responses of these lesions to reserpine and CD-3400 correlate with changes of ionic fluxes in gastric juice.

Acetates↗

PubMed1991

Transsynaptic activity regulates proenkephalin and tyrosine hydroxylase gene expression and the response to reserpine in the hamster adrenal.

Transsynaptic neurogenic activity and reserpine are two signals that cause the proenkephalin (Penk) gene to alter the levels of preproenkephalin (PPenk) mRNA and enkephalin-containing (EC) peptides. In the Syrian hamster adrenal, but not in rat adrenal, both of these signals appear to be positive activators of Penk gene expression. The separate and combined effects of reserpine and denervation on EC peptides and catecholamine systems were investigated in the adrenal of the hamster, a species with relatively high medullary PPenk mRNA and EC peptide levels. Unilateral adrenal denervation resulted in a rapid decrease in PPenk mRNA levels of 54% after 2 days, and by 11 days 90% of Penk mRNA had disappeared. After 4 days both EC peptide and PPenk mRNA levels fell in parallel, whereas total RNA and soluble protein levels were unchanged. Denervation had no effect on TH mRNA levels until 8 days after surgery, and after 11 days both TH mRNA and catecholamine levels had decreased by 35-45%. Reserpine produced a dose- and time-dependent depletion of EC peptides and catecholamines. One day after 5 mg/kg reserpine (given subcutaneously on each of 2 consecutive days), EC peptides were reduced by 80%, norepinephrine by 79%, and epinphrine by greater than 95%. By 4 days after treatment, EC peptides and catecholamines slightly exceeded or had returned to control (concurrent vehicle treatment) values. PPenk mRNA levels, as measured by solution hybridization, were doubled (206 +/- 17%, mean +/- standard error) by day 4. Tyrosine hydroxylase (TH) mRNA levels were increased nearly 7-fold (686 +/- 71%) 24 hr after the first reserpine dose and declined thereafter. Northern blot analysis demonstrated that reserpine did not alter the size of either PPenk or TH mRNAs. Size exclusion chromatography showed a small (20%) reserpine-induced increase in processing of high molecular weight Penk-like peptides. The effects of reserpine, which increases PPenk mRNA, EC peptides, and TH mRNA, were completely blocked by unilateral denervation, whereas the contralateral innervated gland showed the expected responses. The co-localized EC peptide and catecholamine systems, as reflected in their mRNAs, respond differently in both time sequence and magnitude to reserpine and to denervation. Our results support a critical role, in vivo, for transsynaptic mechanisms in the maintenance of the high levels of Penk gene expression in this species and for the positive activation (mediated by reflex neurogenic stimulation) of reserpine on Penk and TH gene expression.

Adrenal Glands↗

PubMed1997

Interactions between a novel cholinergic ion channel agonist, SIB-1765F and L-DOPA in the reserpine model of Parkinson's disease in rats.

SIB-1765F, a novel nicotinic acetylcholine receptor agonist, was tested for its efficacy in attenuating reserpine-induced hypolocomotion in rats. SIB-1765F was administered alone or in combination with L-DOPA and its effects were compared to those of nicotine, d-amphetamine and amantadine in the same conditions. Consistent with previous reports, reserpine-induced hypolocomotion was reversed by L-DOPA (plus benserazide), d-amphetamine and amantadine in a dose-dependent manner and the effect of L-DOPA in reserpine-treated rats was potentiated by amantadine. SIB-1765F also increased the locomotor activity of reserpine-treated rats and potentiated the effect of L-DOPA on reserpine-induced hypolocomotion. The onset of potentiation of L-DOPA by SIB-1765F was rapid (< 5 min) compared to the onset of potentiation by amantadine (> 105 min). Interestingly, nicotine did not attenuate reserpine-induced hypolocomotion nor did it affect the action of L-DOPA on reserpine-treated rats. Biochemical analysis of levels of dopamine and its metabolites, dihydroxyphenylacetic and homovanillic acid, indicated that, in contrast to amphetamine, SIB-1765F did not inhibit dopamine reuptake. The effect of SIB-1765F in reserpine-treated rats was attenuated by alpha-methyl-p-tyrosine, implying that SIB-1765F acts by releasing dopamine from both reserpine-insensitive and reserpine-sensitive pools. Our findings demonstrate that nicotinic acetylcholine receptor agonists may offer a new therapeutic approach to the symptomatic treatment of the motor deficits in patients with Parkinson's disease.

Amantadine↗

PubMed1986

Effect of reserpine on regional cerebral glucose metabolism in control and migraine subjects.

The regional cerebral metabolic rate of glucose metabolism (RCMRGlu) in five headache and six control subjects was measured with positron emission tomography (PET) using the tracer 2-deoxy-D-[1-11C] glucose before and after the administration of reserpine. The short half-life of the carbon 11 tracer made possible a test-retest paradigm wherein each subject served as his own control in assessing the effect of reserpine on RCMRGlu. Thus, measurements were first performed with subjects at rest and subsequently at 1 1/2 hours after the parenteral administration of reserpine (rest-reserpine). In control subjects without history of migraine, reserpine did not induce headache, and, furthermore, PET measurements 1 1/2 hours after drug administration consistently showed a global increase in RCMRGlu over resting values similar to that observed in a normal control (rest-rest) group not receiving reserpine. By contrast, four of the five subjects with migraine began to experience a mild unilateral headache or visual disturbances 1 1/2 hours after reserpine, at which time PET scanning showed a 5% to 30% decline in RCMRGlu below the values that had been measured before reserpine injection, all well outside of the 99% confidence limits of normal variation separately determined on 25 control subjects (rest-rest). There was no apparent laterality, and subjects with a history of either common or classic migraine responded in a similar manner. The difference in percent change in RCMRGlu following administration of reserpine observed in these four subjects with migraine headaches was significantly different over all regions of interest as compared with all six control subjects receiving the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Enhancement by a single dose of reserpine (plus alpha methyl-p-tyrosine) of the central stimulatory effects evoked by dopamine D-1 and D-2 agonists in the mouse.

With the advent of selective dopamine D-1 and D-2 agonists such as SKF38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine HCl) and quinpirole (LY171555, trans-4,4a,5,6,7,8a,9-octahydro-5-propyl-2H-pyrazolo [3,4-g]quinoline), it has become possible to examine the functional role of the two dopamine receptor subtypes as well as their interrelationship. In the present study, we pretreated mice with the granule-depleting agent reserpine (5 mg/kg sc) and tested the mice from 4 h to 10 days later. In all the studies, each mouse also received an injection of the dopamine synthesis inhibitor alpha methyl-p-tyrosine (200 mg/kg ip) 1 h before agonist challenge. Where the reserpine was given 2 or more days before testing, a second dose of reserpine was given 4 h before agonist challenge. While producing no significant locomotor stimulation 4 h after reserpine, SKF38393 produced a dose-dependent increase in coordinated locomotion 24 h and 3 days after the reserpine. Likewise, quinpirole itself produced no significant alteration in activity at 4 h, but significantly increased activity at 24 h and 3 days. The new selective D-1 agonist CY208-243 ((-)-4,6,6a,7,8,12b-hexahydro-7-methyl-indolo [4,3-ab] phenanthridine), unlike SKF38393, produced some increase in activity 4 h after reserpine, but much greater activity was seen 1 and 3 days after reserpine. The enhancement with SKF38393, CY208-243 and quinpirole was most marked 3 days after the reserpine. The behavioural stimulation produced by the mixed D1/D2 agonist apomorphine was also greater 3 days after reserpine pretreatment than after 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1985

Differential effects of reserpine and 6-hydroxydopamine on neuropeptide Y (NPY) and noradrenaline in peripheral neurons.

The effects of 6-hydroxydopamine (6-OHDA) and reserpine pretreatment on peripheral neuropeptide Y (NPY)- and noradrenaline (NA)-containing neurons were studied in guinea-pigs. Ten days after 6-OHDA pretreatment, a 60-80% reduction of the NA content was observed in the right atrium of the heart, stellate ganglion and spleen. The content of NPY-like immunoreactivity (LI) was reduced by about 50% in the heart, not changed in the spleen while it increased to 200% of control in the stellate ganglion. Immunohistochemistry showed a pronounced loss of NPY- and tyrosinehydroxylase (TH)-immunoreactive (IR) nerves in the heart but not in the spleen. Increased NPY-IR was seen in axons and cell bodies of the stellate ganglion. Reserpine pretreatment (thereshold dose 0.5 mg X kg-1) caused a dose- and time-dependent reduction of the content of NPY-LI in the heart. A maximal depletion of NPY-LI (about 80%) was observed 5 days after reserpine. Reserpine pretreatment also reduced the content of NPY-LI in the spleen, while no significant change was observed in the adrenal gland or vas deferens. The levels of NPY-LI increased in the stellate ganglion to about 180% of control 5 days after reserpine. Immunohistochemical analysis revealed an almost total loss of NPY-IR nerve fibres in the heart as well as around blood vessels in the lung and skeletal muscle. No detectable changes were observed in perivascular NPY-IR nerves in the spleen, vas deferens or kidney. TH-IR nerves remained unchanged after reserpine, thus indicating that the observed loss of NPY-IR nerves was due to a depletion of NPY and not a degeneration. No change in the levels of substance P-LI was observed in the right atrium 5 days after reserpine. NA was, in contrast to NPY, markedly depleted in all tissues investigated after reserpine treatment. The depletion of NA was more extensive, and occurred more rapidly and at much lower doses as compared to the effects on NPY-LI. Ligations of the sciatic nerve revealed that NPY-LI was transported axonally with a rapid rate (3 mm/h). Reserpine pretreatment significantly increased the amount of accumulated NPY-IR above the ligation, suggesting an increase in axonal transport. High performance liquid chromatography revealed that the NPY-LI consisted of two major peaks in the stellate ganglia, while only one peak closely corresponding to porcine NPY was seen in the right atrium. In conclusion, 6-OHDA pretreatment depletes NPY-LI in certain terminal regions and increases NPY-LI in ganglia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Alterations of pancreatic amylase secretion in the reserpinized rat model of cystic fibrosis. Effects of cerulein and EGF.

Reserpine treatment resulted in altered enzyme secretion from rat pancreatic acini in response to carbamylcholine and secretin (1,2). This study was undertaken: (1) To evaluate if the alterations caused by reserpine can be prevented by EGF and/or cerulein treatments; (2) To determine the time-course of secretion recovery after reserpine treatment; and (3) To establish if EGF and/or cerulein treatments can accelerate such a recovery after the reserpine treatment. Male Sprague-Dawley rats (250-265 g) were used in these experiments. In experiment I, rats divided into three groups received either reserpine (R) or the reserpine vehicle for the controls (C) and the pair-fed controls (PF) for 7 d. During treatment, PF and R rats were given SC, twice a day, saline, EGF (10 micrograms/kg), cerulein (1 microgram/kg), or both at the same dose. C rats received saline in gelatin. In experiment II, rats were treated for 7 d with reserpine or the vehicle as described in experiment I, were allowed a 30-d recovery period and then were killed. In experiment III, C, PF, and R rats were treated for 7 d as described in experiment I; on the 8th d and for the next 6 d, reserpine rats received saline (reserpine-saline), cerulein, EGF, or both cerulein +EGF at the same dose as indicated in experiment I. C and PF rats received saline in gelatin. After sacrifice, acini were prepared, and amylase dose-response curves to carbamylcholine (Cch) and secretin were established. EGF, cerulein, or their combination given to R rats did not improve the desensitized secretory response to Cch.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗

PubMed1989

Characterization of the interference of T cell activation by reserpine.

It has been suggested that reserpine blocks expression of delayed hypersensitivity (DH) reactions by depleting tissue mast cells of serotonin, thereby preventing a T cell-dependent release of mast cell serotonin necessary to localize and to amplify the DH response. However, reserpine blocks expression of DH in mast cell-deficient mice. Recently, we showed that the ability of reserpine to interfere with the expression of contact sensitivity was independent of an effect on mast cells, but reflected an effort of the drug on effector T cell function. In the present study we evaluated the mechanisms by which reserpine abrogates the expression of T cell functions. By using human peripheral blood mononuclear cells or enriched T cell populations we found that the drug inhibited, in a dose-dependent fashion, the proliferation of T cells after mitogen stimulation. Reserpine also interfered with the mitogen-induced IL-2 production by these cells, but the IL-2 receptor expression, as measured by immunofluorescence, was unaffected. Despite this, in the continuous presence of reserpine, exogenous IL-2 did not bypass reserpine inhibition of PHA-induced proliferation. By using the fluorescent indicator quin-2 we have demonstrated that preincubation with reserpine prevented the increase of cytosolic free calcium, which accompanies PHA-induced proliferative responses of human T lymphocytes. These results identify the sites of action of reserpine in human T lymphocytes and are sufficient to explain its ability to block cell-mediated immune responses in vitro and in vivo.

Antigens, CD↗

PubMed1975

Loss of body weight as a predictor of reserpine-induced amine depletion.

Loss of body weight was proved to be a convenient and reliable way to predict the degree of reserpine-induced amine depletion after i.p. injections of reserpine (2.5, 5 and 10 mg/kg) and it thus helps reduce variability. Two populations of animals were sharply distinguished lying on either side of the 5% cutoff point within the first 24 hr. One group (approximately 20% of all animals) lost less than 5% of their body weight, showed absence of physiological and behavioural effects, a moderate 5-HT depletion and a moderate 5-HIAA increase. These animals were called 'partially reserpinized'. Another group always lost 5% or more of body weight, exhibited the reserpine syndrome as well as a larger extent of 5-HT depletion and 5-HIAA increase. This group comprised 'reserpinized' rats. There were significant correlations between the percent weight loss and the degree of 5-HT depletion and 5-HIAA increase in the group of 'partially reserpinized' animals. The two groups differed also in the time course of amine changes. Dose had no effect in the differentiation of the two groups but did affect the extent of amine depletion. When reserpine was given i.v. or s.c., all animals were 'reserpinized'. The phenomenon of partial reserpinization is discussed.

Animals↗

PubMed1987

Reserpine-induced depletion of neuropeptide Y in the guinea-pig: tissue-specific effects and mechanisms of action.

The effects of treatment with reserpine (5 mg.kg-1, s.c., 24 h prior to sacrifice) or 6-hydroxydopamine (6-OHDA; 250 mg.kg-1, s.c., for 4 days, one week before sacrifice) on the content of neuropeptide Y (NPY)-like immunoreactivity (LI) and noradrenaline (NA) were compared in a variety of tissues from the guinea-pig. Reserpine and 6-OHDA treatment markedly reduced the NA content of all peripheral organs investigated. Reserpine treatment also caused depletion of the content of NPY-LI in larger blood vessels and in organs containing mainly perivascular nerves. Furthermore, reserpine treatment depleted NPY-LI in the heart, spleen and adrenal gland. In other organs dominated by parenchymal adrenergic innervation such as genital organs (vas deferens, uterus) or iris, treatment with 6-OHDA but not reserpine caused significant depletions of NPY-LI. The urinary bladder and gastrointestinal tract seem to be mainly innervated by non-adrenergic NPY-containing neurons resistant to reserpine and 6-OHDA treatment. The content of NPY-LI was elevated in sympathetic ganglia after reserpine treatment while no increase in axonal transport occurred in the sciatic nerve. Cerebellum was the only studied area in the central nervous system where the NPY content was depleted by reserpine or 6-OHDA treatment suggesting presence of NPY-LI in perivascular nerves. The reserpine-induced depletion of NPY-LI in the spleen, kidney and skeletal muscle was prevented by preganglionic denervation. This suggests that enhanced nerve impulse discharge in sympathetic nerves caused a situation where NPY release exceeded the amount which could be replaced by axonal transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Reserpine-induced effects in the adrenergic neuron as studied with cytofluorimetric scanning.

The anterograde axonal transport of norepinephrine (NE), dopamine-beta-hydroxylase (DBH), neuropeptide Y (NPY) and tyrosine hydroxylase (TH) was studied in the rat sciatic nerve after reserpine (10 mg/kg). The histochemical method of Hillarp and Falck was used to study NE and the indirect immunofluorescence technique to study DBH-, NPY- and TH-immunoreactive material (IR), using antisera produced in rabbits. The rats were given reserpine 18 hr, or 1-7 days before sacrifice. Before perfusion fixation one nerve was dissected, frozen and freeze-dried for studies on NE, and the contralateral nerve was then processed for immunofluorescence. The amount of fluorescent material accumulated proximal to a 12 hr crush was quantified in longitudinal sections of the nerve using a cytofluorimetric scanning method. During the early phase after reserpine (18 and 25 hr) the amounts of accumulated NE were undetectable or very low, near control levels at 2 day, and overshooting to 160% of control at 4 d after reserpine. Accumulations of DBH-IR, NPY-IR and TH-IR were also depressed initially to 60-70% of control. DBH-IR and TH-IR thereafter increased to supranormal levels (140% of control) at day 4, while NPY-IR did not exhibit any overshooting but accumulated in the normal range at 2, 4, and 7 days. The results indicate that the amount of material transported distally early after reserpine is depressed. After local vinblastine-treatment of the lumbar sympathetic ganglia the amounts of DBH-IR and TH-IR in the perikarya were markedly lower in reserpine treated rats than in controls, probably due to a decreased perikaryal synthesis of these two enzymes. Rectal temperature in these rats decreased during the initial 10 hr after reserpine by up to 3 degrees C. Thus, the decreased synthesis may be caused by the lowered body temperature, which also may slow down the rate of anterograde axonal transport. The later overshooting in accumulated amounts of NE, DBH-IR an TH-IR gives support to the hypothesis that amine granules containing DBH and NE are produced and transported in supranormal amounts around the 4th day after reserpine. Also, the results indicate that a considerable fraction of TH-IR is transported with organelles, probably amine storage granules, in adrenergic axons. NPY, shown to be localized in amine storage granules, did not overshoot at day 4 after reserpine, in contrast to DBH-IR, TH-IR and NE.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic Fibers↗

PubMed1988

Changes in in vivo binding of 3H-Ro 15-1788 in mouse brain by reserpine.

The effects of reserpine on the in vivo binding of 3H-Ro 15-1788, (Ro 15-1788:ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[1,5a][1,4]benzodiazepine-3-carboxylate) a selective benzodiazepine antagonist, in the mouse brain were investigated. The biodistributions of tracer amounts of 3H-Ro 15-1788 in mice were significantly altered by pretreatment with reserpine (2.5 or 5.0 mg/kg, 24 h before the tracer administration). The time courses of radioactivity in the brain and the blood following i.v. injection of 3H-Ro 15-1788 with carrier Ro 15-1788 were not changed by pretreatment with reserpine, which suggested that the specific binding process might be altered by reserpine. The degree of alteration in the in vivo binding of 3H-Ro 15-1788 seemed to be dependent upon the dose of reserpine and the duration after the treatment of reserpine. The maximum changes in the biodistribution of 3H-Ro 15-1788 were observed at 1 day after injection of reserpine. The body temperature and the brain monoamine contents (dopamine, norepinephrine and 5-hydroxytryptamine) in mice were measured as indicators of pharmacological effects of reserpine, and good relationships to the degree of changes in the biodistribution of 3H-Ro 15-1788 and either the body temperature or brain monoamine contents, were observed. Furthermore, the changes in the biodistribution of 3H-Ro 15-1788 in the reserpinized mice were significantly suppressed by anti-depressant imipramine treatment. These results suggest that it would be possible to detect the in vivo drug interaction with brain benzodiazepine receptors in the living human brain using 11C-Ro 15-1788 and positron emission tomography (PET).

Animals↗

PubMed1982

Multiple effects of reserpine on chromaffin-granule in membranes.

The tranquilizer reserpine has several effects on adrenal medullary chromaffin-granule membrane vesicles (ghosts). At low concentrations (0.20 +/0 0.12 nmol/mg of membrane protein), reserpine inhibits proton-linked epinephrine uptake but does not affect transmembrane pH and electrical potential gradients. Reserpine apparently binds to and blocks the catecholamine translocator. At intermediate concentrations (14.3 +/- 4.8 nmol/mg of membrane protein), reserpine abolishes the ATP-dependent enhancement of 8-anilinonaphthalene-1-sulfonate fluorescence without affecting the ATP-dependent membrane potential. At high concentrations (550 +/- 390 nmol/mg of membrane protein), reserpine stimulates the efflux of epinephrine from preloaded chromaffin-granule ghosts. Because it is highly hydrophobic, reserpine partitions into the membrane and probably exerts a nonspecific detergent-like action. At high concentrations (74 +/- 25 nmol/mg of lipid), reserpine also increases the permeability of phospholipid vesicles to epinephrine. The effectiveness of reserpine in inhibiting epinephrine transport correlates with the reserpine/membrane ratio but not with the molar concentration. This may account for the larger variation in reports of effective reserpine concentrations.

Adenosine Triphosphate↗

PubMed1993

Effects of reserpine on the content and uptake of dopamine and noradrenaline in rabbit arteries.

1. Change with time of the content and uptake of dopamine (DA) and noradrenaline (NA) in the renal, superior mesenteric and femoral arteries and abdominal aorta of rabbit after reserpine administration was examined. Endogenous DA and NA were measured by high performance liquid chromatography coupled with electrochemical detector. 2. A single dose of reserpine (3 mg/kg, i.p.) maximally depleted the endogenous DA and NA contents in the four blood vessels 24 h after the administration; the ratios of reductions were 70-90% and approximately 90% of the normal levels, respectively. The DA contents in all four vessels recovered to the normal level within 4 days after reserpine. However, NA content did not recover to the normal levels within 30 days after reserpine except in the mesenteric artery. 3. The activity of dopamine beta-hydroxylase (DBH) significantly increased in all four blood vessels 1 h after reserpine. Although the DBH activity returned to the normal level after 3 days in the mesenteric artery, it returned within 24 h in the other three vessels. 4. [3H]-Dopamine and [3H]-NA uptake were almost completely depressed 1 h after reserpine. The [3H]-NA uptake in four vessels recovered to the normal level 2-14 days after reserpine, and [3H]-DA uptake recovered after 30-45 days. Thus, the endogenous DA content in blood vessels was completely restored although DA uptake and NA content were still affected. 5. These results suggested that the recovery of stored DA after reserpine was faster than that of stored NA and the recovery of DA uptake after reserpine was slower than NA uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗