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PubMed1989

Influence of splanchnic nerve on reserpine action in avian adrenal medulla.

Reserpine at three doses (0.05, 0.2, and 0.8 mg/100 g body wt) has been injected intraperitoneally to seven unilaterally splanchnic denervated avian species, in order to ascertain the neural regulation of its action in avian adrenal medulla. The adrenomedullary catecholamines (CA) were estimated at 24 hr after reserpine injection. The findings revealed that reserpine at high doses caused 66-92% depletion of total CA from both the innervated and the denervated glands in all the species investigated. The low dose of reserpine in the passerine (common myna and bulbul) birds resulted in 40-84% reduction of both norepinephrine (NE) and epinephrine (E) from the adrenal glands irrespective of its nerve supply. As a contrast, it depleted 60-80% of both NE and E from the innervated glands as compared to 17-43% reduction from the denervated glands in nonpasserine (woodpecker, parakeet, and koel) birds. Interestingly, in other nonpasserine (pigeon and duck) birds, the low dose of reserpine depleted 66-71% of NE from the innervated glands as compared to only 2-13% reduction from the denervated glands. But in these birds, 60-85% depletion of E, however, occurred independent of neural regulation. The findings suggest that at high doses depletion of CA by reserpine is controlled by some nonneurogenic mechanisms. Generally speaking, at a low dose of reserpine, the splanchnic nerve probably modulates depletion of CA from the adrenal medulla of the nonpasserine birds while the same is governed by some nonneurogenic mechanisms in the passerine birds.

Adrenal Medulla↗
PubMed1989

Stimulation of central D1 dopamine receptors reverses reserpine-induced hypothermia in mice.

In mice rendered poikilothermic by a prior (18 h) subcutaneous administration of reserpine (3 mg/kg) the injection of the D1 dopamine agonist SKF 38393 in doses of 1 mg/kg or more increased dose-dependently, the body temperature. The D1 dopamine antagonist SCH 23390, administered subcutaneously, antagonized, with an ID50 of 16 micrograms/kg, the reversal by SKF 38393 of reserpine-induced hypothermia. The intracerebroventricular administration of 1 microgram per mouse of SKF 38393 was sufficient to elevate by about 7 degrees C the temperature of reserpinized mice. It is concluded that stimulation of central D1 dopamine receptors leads to a marked reversal of reserpine-induced hypothermia; this may constitute a new test to investigate interaction of drugs with these receptors. In reserpine-pretreated mice, the dopamine (DA) agonist apomorphine, which stimulates both the D1 and D2 subtypes of DA receptors, increases body temperature according to a mechanism insensitive to the specific D2 DA antagonist sulpiride (Horowski 1978) or the preferential D2 DA antagonist haloperidol (Danielson, Coutts, Keashly and Tang 1985). This observation led us to believe that D1 DA receptors could be involved in the reversal of the hypothermia induced by reserpine. To check more directly the involvement of D1 DA receptors in the reversal of the reserpine-induced hypothermia we have tested the specific D1 agonist SKF 38393 (Setler, Sarau, Zirckle and Saunders, 1978), administered peripherally or intracerebroventricularly and we have studied its interaction with the specific D1 antagonist SCH 23390 (Iorio, Barnett, Leitz, Houser and Korduba, 1983).

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1995

Innervation-independent changes in the mRNAs encoding tyrosine hydroxylase and the norepinephrine transporter in rat adrenal medulla after high-dose reserpine.

To determine whether a trans-synaptic mechanism triggered the effects of reserpine on adrenomedullary mRNAs encoding the norepinephrine transporter and tyrosine hydroxylase, we administered 10 mg/kg reserpine to rats after unilateral splanchnicotomy, and examined their adrenal medullas using quantitative in situ hybridization. Splanchnicotomy did not alter the decrease in norepinephrine transporter mRNA that follows reserpine administration, but diminished the reserpine-induced increase in tyrosine hydroxylase mRNA by almost 80%. Despite the latter effect, reserpine still induced a significant increase in tyrosine hydroxylase mRNA in denervated adrenal medullas, compared to vehicle-treated adrenal medullas. These results show that a trans-synaptic mechanism does not trigger the decrease in adrenomedullary norepinephrine transporter mRNA following reserpine. In addition, an innervation-independent mechanism mediates a portion of the reserpine-induced increase in adrenomedullary tyrosine hydroxylase mRNA.

Adrenal Medulla↗
PubMed1986

Reserpine and the monoaminergic regulation of adrenal dopamine beta-hydroxylase activity.

The systemic administration of reserpine to rats increases adrenal dopamine beta-hydroxylase activity, but is without significant effect on the Km(tyramine). This induction is partially blocked by hemisplanchnicotomy and by impairment of translation. The combined administration of (a) alpha-methyl-p-tyrosine and p-chlorophenylalanine; (b) 6-hydroxydopamine and p-chlorophenylalanine; or (c) alpha-methyl-p-tyrosine and 5,7-dihydroxytryptamine increases adrenal dopamine beta-hydroxylase activity. These results suggest that the simultaneous depletion of central serotonin and catecholamines, as achieved by reserpine alone or by conjoint action of two specific drugs, is necessary for the induction. p-Chlorophenylalanine (intraperitoneal) or 5,7-dihydroxytryptamine (intracerebroventricular or injected into the medial raphe nucleus) increases the effect of reserpine, but the use of a catecholamine-depleting agent with reserpine does not alter the increase of adrenal dopamine beta-hydroxylase obtained with reserpine alone. The potentiation by 5,7-dihydroxytryptamine is abolished by hemisplanchnicotomy, a result that demonstrates neural mediation of its effect. Although intravenous administration of 6-hydroxydopamine alone increases the activity of adrenal dopamine beta-hydroxylase, the combination of this treatment with p-chlorophenylalanine does not elevate it further, as occurs with intracerebroventricular injections; this suggests a specific role of central catecholamine depletion. The serotonin agonists 5-hydroxytryptophan, fenfluramine and 5-methoxy-N,N-dimethyltryptamine abolish the inducing effect of reserpine. This work sheds light on the action of reserpine as inducer and provides evidence for the role of monoaminergic pathways, with net inhibitory effects, that are involved in the regulation of the activity of an adrenal enzyme.

5,7-Dihydroxytryptamine↗
PubMed2004

Effects of gabaergic drugs on reserpine-induced oral dyskinesia.

Recently we have described the antidyskinetic property of the GABA mimetic drugs valproic acid and topiramate on reserpine-induced oral dyskinesia. In this respect, oral dyskinesia has been associated with important neuropathologies. The present study investigates the effects of different doses of the GABA(A) agonist tetrahydroisoxazolopyridine (THIP), of the GABA(B) agonist baclofen as well as of the GABA(A) modulator diazepam on the manifestation of reserpine-induced orofacial dyskinesia. Male Wistar rats received two injections of vehicle or of 1mg/kg reserpine separated by 48 h. Twenty-four hours later, animals were acutely treated with vehicle or THIP (2, 4 or 8 mg/kg), baclofen (1, 2 or 4 mg/kg) or diazepam (1, 2 or 4 mg/kg) and were observed for quantification of oral dyskinesia and open-field general activity. In order to verify the effects of these drugs per se on spontaneous oral movements, male Wistar rats were acutely treated with vehicle, 8 mg/kg THIP, 4 mg/kg baclofen or 4 mg/kg diazepam and observed for quantification of oral dyskinesia. The two highest doses of THIP or of baclofen abolished the manifestation of reserpine-induced oral dyskinesia while the lowest dose of baclofen attenuated it. Diazepam did not modify reserpine-induced oral dyskinesia at any dose tested. The highest doses of these drugs did not modify spontaneous oral movements. Reserpine-induced decrease in open-field general activity was not modified by any of the doses of THIP and diazepam or by the two lowest doses of baclofen. The highest dose of baclofen potentiated the increase in the duration of immobility induced by reserpine. These results reinforce the involvement of GABAergic hypofunction in the expression of oral dyskinesias, and support the potential therapeutic use of THIP and baclofen in the treatment of oral dyskinesias.

Analysis of Variance↗
PubMed2004

Treatment with subthreshold doses of caffeine plus trihexyphenidyl fully restores locomotion and exploratory activity in reserpinized rats.

Trihexyphenidyl (THP) is a drug commonly used to reduce parkinsonian symptoms. An important side effect of this agent is memory impairment. Since caffeine enhances the potency of THP to inhibit haloperidol-induced catalepsy, caffeine may be used as an adjuvant of lower doses of THP, in order to improve its antiparkinsonian effects without causing memory disruption. To further assess the synergism between caffeine and THP, both drugs were tested in reserpinized rats, another preclinical model of Parkinson's disease. Four groups of rats (n = 7) were treated with reserpine (5 mg/kg, i.p.). A control group (n = 7) was treated only with the vehicle for reserpine (dimethylsulphoxide). The spontaneous locomotor behavior was tested 24 h later in a box with infrared sensors, 30 min after receiving one of the following treatments: distilled water (1 ml/kg), caffeine (1 mg/kg), THP (0.1 mg/kg) or caffeine plus THP. The levels of horizontal locomotion (14 +/- 5%) and vertical exploration (15 +/- 10%) were significantly lower in reserpinized rats treated with distilled water, compared with the mean activity values (100%) recorded in animals pretreated only with the vehicle for reserpine. The reserpine-induced hypokinesia was neither reversed by caffeine alone nor by THP alone. However, the combination of caffeine plus THP restored locomotion (141 +/- 19%) and vertical exploration (82 +/- 17%) to levels not significantly different to those of non-reserpinized rats. Moreover, the time-course of locomotion and exploration displayed the characteristic habituation over time, in which short-term memory processes are involved. Also, the thigmotaxis index indicated that the combined treatment did not induce anxiety-like behavior. Hence, these results support the proposal that low, subthreshold doses of caffeine plus THP have the potential to alleviate the motor disabilities in parkinsonian patients, with a low risk of causing anxiety or memory impairment.

Analysis of Variance↗
PubMed2002

Reserpine: interactions with batrachotoxin and brevetoxin sites on voltage-dependent sodium channels.

Reserpine inhibited batrachotoxin-elicited sodium influx in guinea pig brain synaptoneurosomes with an IC50 of about 1 microM. In the presence of brevetoxin the IC50 increased to about 80 microM. Reserpine inhibited binding of batrachotoxinin-A [3H]benzoate ([3H]BTX-B) binding in a complex manner causing a partial inhibition from 0.001 to 0.08 microM, then a rebound stimulation from 0.1 to 0.8 microM, followed by complete inhibition by 80 microM. The stimulation was prevented by the presence of brevetoxin; reserpine then smoothly inhibited binding with an IC50 of about 1 microM. Reserpine at 1 microM slightly reduced the off-rate of [3H]BTX-B binding measured in the presence of veratridine, while at a concentration of 50 microM it enhanced the off-rate, presumably by an allosteric mechanism. Reserpine at 0.3-10 microM elicited a partial inhibition of the binding of [3H]brevetoxin-3. The local anesthetic dibucaine had effects similar to reserpine: It partially inhibited binding of [3H]brevetoxin. The presence of brevetoxin reduced the potency of dibucaine as an inhibitor of batrachotoxin-elicited sodium influx from an IC50 of about 2 microM to an IC50 of about 50 microM. The results suggest that reserpine binds at both a local anesthetic site to cause allosteric inhibition of batrachotoxin-binding and action, but that it also binds to another site causing, like brevetoxin, an enhancement of batrachotoxin-binding and action. Local anesthetics also may bind to the brevetoxin site.

Animals↗
PubMed1977

Effects of reserpine on retention of escape reversal in mice: absence of state-dependent learning.

A discriminated escape training paradigm was used to study the effects of reserpine on learning and memory in mice. Intraperitoneal injection of reserpine before reversal training had no effect on acquisition but did produced a time-and dose-dependent impairment of retention test performance 10 days later. These results suggested that reserpine may have interfered with some aspect of memory storage. Retention impairments observed when a 2.0 mg/kg reserpine injection was given 2 hr before reversal training were not attenuated by readministering the drug before testing, a finding that provides no support for a state-dependency interpretation. Furthermore, animals treated with reserpine exhibited inferior retention of previous training, regardless of the pharmacological state present during that learning. This was interpreted as a drug-induced impairment of memory retrieval. In addition, performance during the initial discriminated escape training session suggested that reserpine may also impair acquisition under some conditions. In the last experiment, it was found that when the catecholamine precursor L-dihydroxyphenylalamine (100 mg/kg) and the indole amine precursor D,L-5-hydroxytryptophan (125 mg/kg) were both given after reserpine treatment, subsequent retention performance was not significantly impaired. The results are discussed in terms of the possible roles of biogenic amines in arousal, learning, and memory.

5-Hydroxytryptophan↗
PubMed1990

Induction of responsiveness of rat diaphragm to ovine growth hormone after administration of reserpine.

The diaphragm of the pituitary intact rat is insensitive to the insulin-like effects of growth hormone unless weanling animals are used, and even then these effects are not achieved reliably. We report here that an intraperitoneal injection of reserpine is able to induce consistent responsiveness to ovine growth horomone (oGH) in hemidiaphragms from 20-27 day old rats as assessed by stimulation of 3H-AIB transport and 14C-phenylalanine incorporation into protein. Maximal stimulation of 3H-AIB transport (approximately 40%) can be elicited by addition of oGH (5 micrograms/ml) to hemidiaphragms after a 2 mg/kg injection of reserpine given 5 h prior to sacrifice. The degree of stimulation does not alter significantly if the rats are sacrificed 3, 5 or 12 h after administration of reserpine, although it decreases by 24 h. Administration of reserpine 3 h before sacrifice also leads to a 50% increase in 14C-phenylalanine incorporation into protein in rat diaphragms in response to the addition of oGH (5 micrograms/ml). The induced sensitivity to oGH is not due to inhibition of GH secretion by reserpine as demonstrated by RIA of plasma GH. Addition of a monoclonal antibody to the GH receptor (MAb263) did not result in a stimulation or inhibition of 3H-AIB uptake or stimulation of protein synthesis in reserpinized rat hemidiaphragms. These results suggest that reserpine can induce tissue responsiveness in rats 20-27 d.o. independent of plasma GH levels. Our results also imply that the type 1 GH receptor of Barnard, Bundesen, Rylatt and Waters (1985) does not mediate the insulin like actions of GH on rat diaphragm.

Aminoisobutyric Acids↗
PubMed1994

Reserpine-induced cell transformation without detectable genetic effects in Syrian hamster embryo cells in culture.

Reserpine, a naturally occurring rauwolfia alkaloid, used mainly as an antihypertensive drug, was examined for its ability to induce cell transformation and genetic effects in Syrian hamster embryo (SHE) cells in culture. Treatment of SHE cells with 2 micrograms/ml of reserpine had no effect on cell growth, while 4 micrograms/ml of reserpine reduced the growth rate slightly and 8 micrograms/ml resulted in a significant inhibition of cell growth. Reserpine at doses of 4-8 micrograms/ml for 48 h induced a dose-related increase in morphological transformation of the cells. Reserpine-transformed colonies were morphologically indistinguishable from colonies transformed with benzo[a]pyrene (B[a]P) or other chemical carcinogens. Over the dose range that resulted in cell transformation, treatment of SHE cells with reserpine failed to induce any detectable gene mutations at two genetic loci, chromosomal abnormalities including structural and numerical changes, or DNA adduct formation. These findings indicate that reserpine may have carcinogenic potential by unknown mechanisms that do not include direct induction of gene and/or chromosome mutations.

Aneuploidy↗
PubMed1988

Reserpine treatment increases viscosity of fluid in the epididymis of rats.

Reserpine treatment in rats induces morphological and functional disturbances in exocrine glands which resemble those produced by cystic fibrosis. The general feature is a decrease in fluid secretion with a rise in mucous concentration and altered electrolyte composition. Chronically reserpinized rats have therefore been used as an animal model for the disease. It is known that cystic fibrosis men are infertile due to obstruction of the epididymal duct with inspissated material, a phenomenon that may be secondary to abnormal electrolyte and water transport in the epididymis. Male rats were treated with reserpine (0.5 mg/kg/day) for 12 to 14 days. At the end of the treatment, epididymal fluids were flushed out from the cauda epididymidis for measurement of spermatocrit, viscosity, total protein concentration, sperm concentration and motility. It was found that reserpine treatment caused a rise in viscosity (by 40%), spermatocrit, sperm concentration, and protein concentration. These changes were observed in the epididymis of rats that had been efferent duct-ligated before reserpine treatment. Despite a rise in viscosity of the fluid bathing the spermatozoa, the viability of the stored spermatozoa was apparently normal. Spermatozoa were able to initiate forward motility when suspended in a sodium-containing medium. Testis fluid secretion measured by weight gain after efferent duct ligation for 16 h was not affected by reserpine treatment. The change in viscosity probably was due to a decrease in fluidity in the epididymis. It is concluded that reserpine treatment in rats produced changes in the exocrine functions of the epididymis similar to those seen in other exocrine glands.

Animals↗
PubMed2002

Long-term low-dose treatment with reserpine of cholesterol-fed rabbits reduces cholesterol in plasma, non-high density lipoproteins and arterial walls.

The effects of long-term low-dose treatment with reserpine on plasma lipoproteins and arterial cholesterol were determined in cholesterol-fed rabbits. Hepatic low-density lipoprotein (LDL) receptors; uptake of LDL by liver, heart, and kidneys; plasma fibrinogen; blood pressure; and heart rate were also determined. Reserpine at 43 microg/kg. d was continuously infused subcutaneously via implanted minipumps for 6 weeks into conscious unrestrained male New Zealand White rabbits (n = 5) fed a 0.2% cholesterol-enriched diet. Compared with controls, reserpine (n = 4) significantly reduced the elevated levels of plasma total cholesterol and esterified and unesterified cholesterol throughout the study, and at 6 weeks of treatment these reductions were 42, 41, and 49%, respectively. The increased cholesterol in the aortic walls (n = 5) produced by the atherogenic diet was reduced by 73% (p < 0.004) and 125I-tyramine cellobiose-labeled LDL by 67 to 86% (0.05 < p <0.004), respectively. The aortic intimal-medial thickness ratio was reduced by 70%. The decrease in elevated plasma total cholesterol was mainly due to cholesterol reductions in both LDL (41%) and non-high density lipoprotein (HDL) of density < 1.019 g/ml (51%). HDL cholesterol and triglyceride levels were unchanged. Reserpine had no significant effects on the clearance of 125I-tyramine cellobiose-LDL from plasma and there was a trend towards an increase in hepatic LDL receptor expression. Heart rate was decreased by 28%. There were no significant effects on blood pressure, liver and heart lipids, hematocrit, or plasma fibrinogen. The results suggest that treatment of cholesterol-fed rabbits with reserpine at a low dose over a long period prevents increases in plasma atherogenic lipoproteins. Reserpine decreases the cholesterol in aortic walls and the intima-media thickness ratio. This anti-atherosclerotic effect of reserpine may have therapeutic implication.

Animals↗
PubMed1992

Reserpine-induced processing of chromogranin A in cultured bovine adrenal chromaffin cells.

The effect of reserpine on the processing of the secretory granule protein chromogranin A (CgA) in isolated bovine adrenal chromaffin cells was investigated using two radioimmunoassays employing site-specific antisera. The two antisera were directed against closely associated regions of the CgA molecule which would be exposed by specific processing: antiserum L331 was raised against the C-terminus of the regulatory peptide pancreastatin, and the second antiserum, L300, was raised against the synthetic peptide [Tyr0]CgA306-313 (YLSKEWEDA), a sequence that lies immediately C-terminal to pancreastatin and adjacent to a dibasic amino acid cleavage site. Chronic reserpine treatment of chromaffin cells produced a time- and dose-dependent increase in processing, as demonstrated by an increase in pancreastatin- and YLSKEWEDA-immunoreactivity (ir). The reserpine-induced rise in pancreastatin-ir was due predominantly to an increase in pancreastatin 1-47, whereas the rise in YLSKEWEDA-ir was due to increases in three polypeptides: a 51-kDa YLSKEWEDA-ir polypeptide, CgA297-313, and CgA248-313. The latter predominated. The action of reserpine on both pancreastatin- and YLSKEWEDA-ir was found to be largely inhibited by the protein synthesis inhibitor cycloheximide. The results show that treatment of isolated chromaffin cells with reserpine induces both the selective proteolytic processing and peptidyl-glycine amidation of CgA and its derived fragments. As reserpine has a similar effect on proenkephalin in chromaffin cells, the results suggest that reserpine induces a general increase in the activity of the processing enzymes, partially by an increase in protein synthesis.

Adrenal Glands↗
PubMed1969

Histamine formation in rat gastric mucosa and lung after injecting reserpine or adrenaline.

1. In rats the effect of reserpine, adrenaline and gastrin on the histamine forming capacity (HFC) of gastric mucosa and lung was examined.2. Intraperitoneal reserpine as well as subcutaneous adrenaline produced a great increase in HFC of gastric mucosa but a great decrease in HFC of lung. After reserpine the HFC of lung was almost abolished.3. As the HFC changes produced by reserpine occurred also after demedullation of the suprarenals--the changes in the mucosa were in fact accentuated--release of the medullary hormones by the reserpine does not account for these changes.4. Subcutaneous gastrin caused a great increase in HFC of the gastric mucosa but did not affect the HFC in lung.5. The possible role of release of gastrin and corticosteroids for the reserpine-induced HFC changes is discussed because it is known that reserpine releases gastrin and corticosteroids and that cortisone produces HFC changes in gastric mucosa and lung.

Adrenal Cortex Hormones↗
PubMed1973

Influence of reserpine-induced depletion of noradrenaline on the negative feed-back mechanism for transmitter release during nerve stimulation.

1. The effects of depletion of endogenous noradrenaline by reserpine-pretreatment on [(3)H]-noradrenaline overflow elicited by nerve stimulation were determined in the isolated nerve-muscle preparation of the cat's nictitating membrane.2. Reserpine pretreatment (0.3 mg/kg, s.c., 4 days prior to the experiment) reduced the noradrenaline levels in the smooth muscle of the nictitating membrane to about 10% of the control values while granular retention of [(3)H]-noradrenaline had recovered to nearly 40% of the controls.3. In the reserpine-pretreated tissue the fraction release per shock induced by nerve stimulation was 2.2-fold higher than the value obtained in the untreated tissues. This effect was correlated with the degree of depletion of the noradrenaline stores rather than with the decrease in the response of the effector organ.4. Phenoxybenzamine, 2.9 muM reduced the responses to nerve stimulation to the same extent in control and in reserpine-pretreated tissues. Yet, this concentration of phenoxybenzamine increased by 13-fold the overflow of the labelled transmitter in the controls and only by 3-fold in reserpine-pretreated tissues.5. The decrease in effectiveness of phenoxybenzamine in enhancing transmitter overflow after reserpine-pretreatment appears to be due to the decrease in the total release of the transmitter.6. The results obtained support the view that in reserpine-pretreated tissues decreased transmitter output reduces the activation of the presynaptic alpha-adrenoceptors which mediate the negative feed-back mechanism that regulates transmitter release by nerve stimulation.

Animals↗
PubMed1975

Effects of reserpine on the adrenal medulla of the spontaneously hypertensive rat.

1. Reserpine administration resulted in a larger initial decline in adrenal catecholamines in spontaneously hypertensive rats (SHR) than in normotensive Wistar rats (NWR); the difference was eliminated by pretreatment with cholisdondamine. 2. Reserpine also produced a larger increase in SHR catecholamines and dopamine beta-hydroxylase several days later; chlorisondamine pretreatment did not prevent the increases, although it did slightly slow the increases. 3. Vesicles from SHR, or NWR incubated with reserpine in vitro demonstrated equivalent inhibition of adenosine 5'-triphosphate (ATP)-Mg-2+-stimulated adrenaline uptake. 4. Recovery of uptake was more rapid in SHR than in NWR after reserpine inhibition, and this was associated with a burst of new vesicle synthesis in the SHR; chlorisondamine pretreatment reduced the number of new, immature vesicles in reserpine-treated SHR. 5. Both SHR and NWR secreted equal proportions of their adrenal catecholamine contents after nicotine administration. 6. These data suggest that the sympatho-adrenal system of the SHR exhibits an enhanced reflex response to reserpine but that reserpine is equally effective in SHR and NWR in producing blockade of vesicular catecholamine transport; these alterations can affect markedly the actions of autonomic drugs in the SHR.

Adrenal Medulla↗
PubMed1977

The effects of reserpine and 6-hydroxydopamine on the concentrations of some arylakylamines in rat brain.

1 The concentrations of p- and m-tyramine were measured in the caudate nucleus of the rat brain following subcutaneous injection of reserpine or intraventricular injection of 6-hydroxydopamine, beta-Phenylethylamine was analysed in the hypothalamus after reserpine. 2 Endogenous levels of p-tyramine and m-tyramine in the caudate nucleus, and beta-phenylethylamine in the hypothalamus were 8.02, 2.25 and 2.52 ng/g respectively. 3 Tyramine concentrations were reduced to less than 20% of control values one day after a reserpine injection of 1 or 10 mg/kg. A single dose of reserpine (0.4 mg/kg) significantly decreased the content of both tyramines in the caudate nucleus. The effects became apparent as early as 45 min after drug case of m-tyramine. 4 The hypothalamic content of beta-phenylethylamine was unaffected by reserpine. 5 Ten days after an intraventricular injection of 6-hydroxydopamine (250 mug), p- and m-tyramine concentrations in the caudate nucleus were significantly below control levels. 6 The results suggest that p- and m-tyramine may be stored by an intraneuronal reserpine-sensitive storage mechanism. Alternatively, the tyramines may replace some of the catecholamines from their storage granules and then be released as false transmitters by the nervous impulse. The observed changes in tyramine levels might also the fact that these amines may be metabolically related to another amine which is stored in reserpine-sensitive granules.

Animals↗
PubMed1979

Short and long-term effects of reserpine on the concentration of 1-(4-hydroxy-3-methoxyphenyl)-ethane-1,2-diol (MOPEG-SO4) in the brain of the rat.

1 Reserpine (1.25 mg/kg i.p.) induced an increase (172% of controls) in the concentration of 1-(4-hydroxy-3-methoxyphenyl)-ethane-1,2-diol sulphate (MOPEG-SO(4)) in rat brain and a decrease in the noradrenaline (NA) concentration to 50% of controls 2 h after injection. At this time the MOPEG-SO(4)/NA ratio was 0.28. Thereafter the MOPEG-SO(4) concentration declined and the NA concentration decreased further to 28% of control.2 Higher doses of reserpine (2.5 and 5 mg/kg i.p.) did not induce a larger increase in the concentration of MOPEG-SO(4).3 While a second dose of reserpine (1.25 mg/kg i.p.) given 24 h after the first did not increase the MOPEG-SO(4) concentration, amphetamine (5.0 mg/kg i.p.) administration or electrical stimulation significantly increased the concentration of MOPEG-SO(4).4 NA and MOPEG-SO(4) concentrations were examined during 5 days after a single dose of reserpine (1.25 mg/kg i.p.). While the concentration of NA started to return towards normal after 24 h, that of MOPEG-SO(4) remained at approximately 70% of controls during the entire period.5 The probenecid-induced accumulation rate of MOPEG-SO(4) was significantly lower 3 and 4 days after reserpine and returned to the control value on the fifth day. At this time the concentration of NA had reached 50% of the control value.6 These experiments indicate that MOPEG-SO(4) is not the major metabolite of NA during the initial phase of reserpine-induced NA release. Reserpine acts on the storage pool while amphetamine (like electrical stimulation) acts on the functional pool. During the first phase of post-drug recovery, there is a clear decrease in NA output which appears to be regulated by the concentration of NA in the storage pool.

Animals↗