Influence Of Reserpine Research Articles

Quinolinic acid: effects on brain catecholamine and c-AMP content during L-dopa and reserpine administration.

The catecholamine content in rat brain tissue was determined following the administration of quinolinic acid alone or combined either with L-dopa and decarboxylase inhibitor or reserpine. Quinolinic acid alone decreased the levels of dopamine and noradrenaline, as well as those of c-AMP, and increased those of adrenaline. Treatment with L-dopa/decarboxylase inhibitor reversed the suppressing effect of quinolinic acid on dopamine, but not on noradrenaline. Reserpine alone depleted the contents of dopamine, noradrenaline and adrenaline. It could be concluded from the effects of quinolinic acid and reserpine given together that quinolinic acid suppresses the depletion of amines induced by reserpine. It has been demonstrated that quinolinic acid leads to injuries of nerve-cell bodies in pars compacta of the substantia nigra and in the striatum. Quinolinic acid is a natural metabolite of tryptophan, normally occurring in the liver, kidney and brain (Wolfensberger et al. 1983; Moroni et al. 1984). This compound exhibits convulsant and neuron excitant properties (Stone et al. 1987). It induces a selective pattern of neuronal degeneration both at the site of intracerebral injection (Schwarcz et al. 1983; Stone et al. 1987) and after general (intracardiac) administration (Beskid and Markiewicz 1988). The ability of quinolinic acid to produce neurotoxicity was greater in the striatum than in other parts of the brain. This prompted us to study catecholamine and c-AMP levels in rat brain tissue following quinolinic acid and L-dopa administration, as well as the influence of reserpine on quinolinic acid action.

The synthesis of NPY and DBH is independently regulated in adrenergic nerves after reserpine

A newly developed cytofluorimetric scanning technique was applied in a pharmacological study to investigate the influence of reserpine (10 mg/kg) on the axonal transport of norepinephrine (NE), dopamine-beta-hydroxylase (DBH), tyrosine hydroxylase (TH), and neuropeptide Y (NPY)-like immunoreactivities (LI) in the adrenergic axons of the sciatic nerve of rat. Early after reserpine (18 hr and 24 hr after the reserpine injection) the amounts of NE accumulated proximal to a 12-hr crush were nil or very low, as observed in earlier studies. DBH-LI, TH-LI, and NPY-LI accumulations were also depressed but only to about 50% of control accumulations. This decrease in amounts of transported substances was probably caused by a decrease in protein synthesis and also a lowered velocity of fast axonal transport initially after reserpine, when body temperature is low. The amounts of accumulated NE, DBH-LI, TH-LI, and NPY-LI were normalized around day 2 after reserpine, but on day 4 NE, DBH-LI, and in some rats also TH-LI accumulated in supra-normal amounts. However, NPY-LI accumulations were normal, indicating that DBH, but not NPY, was trans- synaptically induced in rat sympathetic neurons, and that the biochemical composition of axonally transported organelles is altered for some days after reserpine.

Intraneuronal dopaminergic action of cocaine and some of its metabolites and analogs

The present study investigated the actions of cocaine and some of its metabolites and analogs upon the synaptosomal (P 2) synthesis and release of dopamine appearing from [ 14C]phenylalanine. Also examined was the influence of reserpine upon these actions of cocaine. The P 2 preparations from the rat caudate nucleus were incubated with the drugs for [ 14C]phenylalanine and, after filtration, the particulates and medium fractions were analyzed for [ 14C]dopamine and [ 14]phenylalanine. Labelled dopamine in the medium was taken as a measure of its release by any addition of drug. Cocaine, norcocaine and the synthetic cocaine analogs WIN 35428 and WIN 35-065(2) each stimulated both the total (medium plus particulates) formation and the release of dopamine, while benzoylecgonine and ecgonine were without effect. Reserpine inhibited the synthesis and enhanced the release of dopamine. An addition of reserpine blocked the stimulating effect of cocaine, norcocaine, WIN 35428 and WIN 35-065(2) on synthesis and furthermore, these drugs had, in the same experiments, inhibitory effects on the synthesis, additive to the reserpine-induced inhibition. Benzoylecgonine and ecgonine were only weakly inhibitory in the presence of reserpine. Stimulation, rather than additive inhibition, by cocaine was observed in the presence of exogenous dopamine, and amphetamine increased the synthesis in the presence of either reserpine or added dopamine. Pretreatment of rats with reserpine also blocked the stimulation of synthesis by cocaine and WIN 35428. The uptake of labelled substrate was not affected by addition of drug, or by the pretreatment.

Reserpine Inhibits Rat Anterior Pituitary Hormone Secretion in Vitro: Effects on GH, TSH, and LH

We have extended our observations on the ability of reserpine to inhibit secretion of anterior pituitary hormones in vitro. The release of newly synthesized [3H]GH and radioimmunoassayable TSH and LH from female rat anterior hemipituitary glands was measured after 5 hr incubation in [3H]leucine in the presence or absence of reserpine. Reserpine, 9 μM, blocked the release of each hormone stimulated by 50 mM K+ but not basal hormone secretion. Stimulation of [3H]GH release by 10 μM PGE1, or 5 mM dbcAMP was not affected by 5 μM reserpine, while stimulation of TSH release by 70 nM TRH was significantly blunted with 5 μM reserpine. The influence of reserpine on pituitary hormone secretion may define a pattern suggesting that the drug interferes with utilization of the extracellular but not the intracellular calcium mobilized during the secretory process.

The influence of reserpine on nitrogen metabolizing enzymes in chick liver

Reserpine, a Rauwolfia alkaloid, was shown to increase activity of the hepatic nitrogen metabolizing enzymes xanthine dehydrogenase, purine nucleoside phosphorylase, and tyrosine aminotransferase, when administered orally to young chicks. Using immunochemical techniques, this increase in xanthine dehydrogenase was shown to result from an enhanced de novo enzyme synthesis. The response pattern of the three enzymes to reserpine follows the same pattern to induction by high dietary protein suggesting that a common mode of action may be involved in the regulation of these enzymes. α-Adrenergic blockers, phentolamine and phenoxybenzamine, effectively prevented the increased enzyme activities caused by administration of reserpine.

The role of calcium in the mechanism of changes in vascular reactivity due to reserpine

Under the influence of reserpine there is a marked decrease in the calcium concentration in segments of the distal aorta and femoral arteries of rabbits, incubated in salt solution. These changes develop parallel with changes in the character of responses of the vascular segments to direct electrical stimulation (weakening of the effects of contraction, followed by relaxation). A decrease in the calcium concentration in the vascular wall is suggested as one cause of the change in vascular reactivity.

Ultrastructural analysis of the action of reserpine on the brain neuroendocrine system of the wax moth, Galleria mellonella L., Lepidoptera.

This study concerns the influence of reserpine on the fine structure of peptidergic neurosecretory cells in the pars intercerebralis of Galleria mellonella, and of neurons containing smaller dense-cored vesicles (presumed to be aminergic) localized in the same area of the brain. The drug, administered in doses of 125 microgram and 250 microgram per g of insect body weight, reduces both the amount and the electron opacity of the dense-cored vesicles with a diameter of 60--80 nm in the neuronal perikarya as well as their terminals. Simultaneously, this treatment evokes an abnormal accumulation of secretory granules within the perikarya of peptidergic neurosecretory cells belonging to three types. This accumulation of secretory material is followed by some changes in the fine structure of these cells. One (fourth) type of neurosecretory cells seems to be insensitive to reserpine action. Participation of the aminergic system in the regulation of the secretory activity of some populations of peptidergic neurosecretory neurons of the insect brain is postulated.

A Pharmacological Analysis of Cushing's Response in Rats

Cushing demonstrated that acute elevation of intracranial pressure (ICP) to levels above the initial mean arterial pressure (MAP) provokes an increase in blood pressure. This effect, now known as the Cushing response, is accompanied by tachycardia. The pressor response during the Cushing reflex is a result of a strong sympathetic discharge. This chapter presents a pharmacological analysis of Cushing's response in rats. The blood pressure response after acute elevation of the intercranial pressure is studied in anaesthetized rats. After establishing an ICP/blood pressure curve, the chapter studies the influence on this response of bilateral vagotomy, with and without atropine pretreatment and that of L(—)propranolol, practolol, phentolamine, piperoxane, clonidine, and hydralazine. The influence of reserpine, 6-hydroxydopamine (6-OHDA), and guanethidine, with or without bilateral adrenalectomy, is studied as well. The results suggest that in order to be able to inhibit a pressor response due to a rise in ICP, both the peripheral sympathetic system and the adrenal medulla should be dysfunctional.

Influence of Reserpine on the Levels of B_6 Vitamers in Mouse Brain

Influence of Reserpine on the Levels of B_6 Vitamers in Mouse Brain

Variations in melanin and riboflavin content of amphibian liver under the influence of reserpine and amphetamine.

By means of paper chromatography, Lactobacillus casei test and the staining method with the Feulgen reaction, the effects of reserpine and amphetamine on riboflavin and melanin were studied in the liver of Triturus cristatus. It was demonstrated that the concentrations of both melanin and riboflavin can be altered by the influence of these drugs. From the results obtained it is suggested that riboflavin shows a correlation with the density of melanin.

Influence of reserpine on high calcium perfusion of thyro-parathyroid glands in dogs.

Perfusion of the thyro-parathyroid glands in the dog with calcium-rich blood led to a significant decrease (P less than 0.001) in the systemic plasma calcium level. On the other hand, injection of reserpine (0.2 mg/kg ip) 16 and 2 h prior to infusion of hypercalcemic blood into thyro-parathyroid glands did not alter the systemic plasma calcium level significantly (P less than 0.05). This result provides evidence that reserpine blocks the release of hypocalcemic factor from the thyro-parathyroid glands in response to perfusion of high concentrations of calcium.

The effects of L-DOPA, serotonin, reserpine and chlorpromazine on the daily rhythm of fluorescent intensity in leucocytes and blood platelets

1) The rhythmic fluctuation of fluorescent intensity of leucocytes and platelets of rats was modified by the administration of some drugs such as L- DOPA, serotonin, reserpine and chlorpromazine. Timing of administration was determined to get clearcut results. The different results were expected by the administration of drugs at the other time of day. 2) The administration of L-DOPA enhanced the fluorescent intensity of leucocytes and platelets, and the tincture of them tended strongly to be green at 4 to 10 h after the treatment. The administration of serotonin suppressed the fluorescent intensity of leucocytes temporarily, but inversely enhanced the intensity of platelets significantly. Reserpine and chlorpromazine had a similar suppressive effect on the fluorescent intensity of leucocytes and platelets within 30 h after the treatment. Compared with them, the influence of reserpine was stronger than that of chlorpromazine. 3) In fact, these drugs made an marked influence on the rhythmic fluctuation of fluorescence intensity in leucocytes and platelets, but the physiological rhythmicity was remained in the ground of modified fluctuation of rats which were treated by those drugs.

Simultaneous measurement of atrial and ventricular pacemaker activity.

The isolated perfused rat heart with surgically-induced heart block was used to determine the effect of drugs on the activity of the atrial and ventricular pacemaker simultaneously. Complete atrio-ventricular dissociation was produced by tying a ligature around the Bundle of His under direct vision. Pacemaker rates remained stable for at least 2 hours. Perfusion of the hearts with quinidine produced a decrease in the rate of both the atrial and ventricular pacemaker. The ventricular pacemaker was more susceptible to the depressant action of quinidine than the atrial pacemaker.

The effect of dibutyryl 3'5'-cyclic AMP on the cardiac pacemaker, arrested with reserpine and alpha-methyl-tyrosine.

Spontaneous activity of the isolated cardiac pacemaker, investigated by means of microelectrodes, ceases under the influence of reserpine or α-methyl p-tyrosine. It may be restored either by washing the preparation with Tyrode solution or by adding catecholamines to the perfusing fluid containing reserpine or α-methyl p-tyrosine. In the majority of experiments it was also possible to restore the spontaneous activity with dibutyryl cyclic AMP added to the perfusing fluid containing one of the two inhibitors mentioned above.

The influence of reserpine on incorporation of 3 H-thymidine into mouse liver DNA.

Der Einbau von3H-Thymidin in die DNA der Leber von weiblichen weissen Mausen wurde 60 h nach der Verabreichung von 2 mg/kg Reserpin und ausserdem 60 h nach Futterentzug an nicht reserpinisierten Tieren gemessen. Reserpin fuhrt unabhangig von der unter dieser Substanz auftretenden Hypothermie und Anorexie zu einer Hemmung des3H-Thymidin-Einbaus in die DNS der Leber um etwa 60%.

Changes in the Tracheal Respiratory Mucosa of Rats Following Experimentally Induced Burns of the Skin. Influence of Reserpine

The tracheal respiratory mucosa in rats sacrificed on the second and fourth day following experimentally induced burns of the skin was submitted to histological study. Pathological changes were found in the respiratory mucosa of all animals with hepatic and kidney damage. In a second experiment the attempt was made to prevent kidney and liver lesions by administration of “Reserpin”. The correlation between kidney and liver lesion and the changes in the respiratory mucosa are discussed.

The depletion of the granules of argyrophile cells of dog duodenum by reserpine

The influence of reserpine on the argentaffin and non-argentaffin argyrophile cells of the duodenum has been studied in 8 dogs. In two dogs that were given 5 mg/kg of reserpine there was a complete disappearance of both types of cells. In another dog given 5 mg/kg and in dogs given 2.5 mg/kg and 1 mg/kg reserpine, the number of argentaffin cells was reduced to almost nil while the number of non-argentaffin argyrophile cells showed a statistically significant reduction. The degree of depletion of non-argentaffin argyrophile cells was proportional to the dose of reserpine given. The findings show that the non-argentaffin argyrophile cells are closely related to 5-hydroxytryptamine and their distinction from argentaffin cells is only a quantitative one.

5-Hydroxytryptamine uptake and release in relation to aggregation of rabbit platelets.

1. The aggregation of blood platelets was measured in vitro at different time intervals after the addition of 5-hydroxytryptamine (5-HT) or of reserpine to platelet-rich plasma of untreated rabbits and of rabbits injected with reserpine and 5-HT, i.e. while the platelets were taking up 5-HT or releasing it under the influence of reserpine.2. When 5-HT was added to stirred platelet-rich plasma the platelets aggregated reversibly within 1 min. The velocity of aggregation increased with 5-HT concentrations of 0.1-30 muM and decreased with higher concentrations.3. (-)-Adrenaline, which alone did not produce aggregation, markedly accelerated the aggregation caused by 5-HT. The acceleration was greatest when 5-HT and adrenaline were added simultaneously.4. 5-HT added to the platelet-rich plasma in amounts that exceeded the 5-HT capacity of the platelets progressively diminished the velocity of aggregation produced by 5-HT plus adrenaline until aggregation was completely inhibited. Smaller amounts of 5-HT produced a transient inhibition of aggregation.5. The aggregation of platelets from reserpinized rabbits was inhibited by less 5-HT than the aggregation of platelets from normal rabbits.6. (-)-Adrenaline aggregated platelets of untreated rabbits but not those of reserpinized rabbits or of rabbits injected with 5-HT when reserpine was added in vitro 1-30 min previously.7. Platelets obtained from rabbits treated first with reserpine and subsequently injected with 5-HT were not aggregated by 5-HT plus adrenaline. During incubation in vitro these platelets progressively recovered their aggregability but this recovery was delayed by the monoamine oxidase inhibitor Pargyline.8. Imipramine in concentrations which did not influence platelet aggregation by adenosine diphosphate (ADP) abolished aggregation produced by 5-HT or by 5-HT plus adrenaline.9. The inhibitory effect of adenosine on platelet aggregation was concentration-dependent and similar whether aggregation was produced by ADP, 5-HT or 5-HT plus adrenaline.10. It is proposed that aggregation brought about by 5-HT is connected with its active uptake into the platelets and is caused by ADP formed from ATP during the active uptake of the amine. When 5-HT is no longer actively taken up, it also ceases to cause or to potentiate aggregation.

Effect of prolactin on the “seminal vesicles” and neural regulation of prolactin secretion in the catfish Heteropneustes fossilis (Bloch)

The effects of testosterone propionate, ovine prolactin, and ovine growth hormone in stimulating the seminal vesicles of catfish have been studied. Prolactin or testosterone propionate alone had no significant effect on the atrophic seminal vesicles of intact or hypophysectomized catfish. Intact catfish pretreated with human chorionic gonadotropin and then administered prolactin had heavier and secretory seminal vesicles. Prolactin or growth hormone induced significant weight increments and secretory activity in the androgen-primed seminal vesicles of hypophysectomized catfish. In hypophysectomized catfish, maximum response was obtained after simultaneous administration of testosterone propionate, prolactin, and growth hormone. The data indicate that while an additive response is obtained by simultaneous administration of testosterone propionate and prolactin or of testosterone propionate and growth hormone, treatment with all three hormones at the same time resulted in marked synergism. The influence of reserpine in inducing prolactin release from the pituitaries of male intact catfish was studied during the postspawning period when the seminal vesicles undergo seasonal regression. The results indicate that treatment with testosterone propionate or prolactin alone in the early postspawning period (October) did not renew secretory activity in the seminal vesicles, whereas reserpine alone or reserpine and testosterone propionate induced significant secretory activity in the seminal vesicles. Since reserpine alone or reserpine plus testosterone propionate bring about secretory activity in the seminal vesicles, it is inferred that reserpine induced the release of prolactin from the pituitary. In the pituitaries of control and of prolactin-treated animals there was paucity of erythrosinophils whereas in reserpine-treated animals pituitaries had an abundance of erythrosinophils. Reserpine did not have a direct effect on the seminal vesicles as evidenced by its inability to stimulate secretory activity in the seminal vesicles of hypophysectomized catfish. The above findings indicate that the neural control of prolactin secretion in the catfish is presumably accomplished by an inhibitory mechanism similar to that demonstrated in the mammals.

Influence of reserpine on the pituitary content of melanocyte-stimulating hormone and on hypothalamic factors which affect its release.

SUMMARY The melanocyte-stimulating hormone (MSH) content of whole toad pituitary glands decreased upon treatment with reserpine. With daily injections the values remained low for 1 week but regained normal levels after 2 weeks in spite of an increased secretion of MSH as indicated by darkening of the skin. In rats a drop in pituitary MSH content also occurred after reserpine injection but normal values were found after 7 and 14 days of treatment. MSH-releasing factor found in stalk-median eminence tissue of normal male rats was not present in the reserpine-injected animals, but after 7 days of treatment an increase in MSH-release-inhibiting factor (MSH-R-IF) was demonstrated. MSH-R-IF was also found to have increased in female castrated rats after 2 days of treatment with reserpine. It is concluded that reserpine permits the secretion of pituitary MSH by blocking the release of MSH-R-IF, which accumulates in the hypothalamic neurones.