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PubMed1994

Large dense-core vesicles in rat adrenal after reserpine: levels of mRNAs of soluble and membrane-bound constituents in chromaffin and ganglion cells indicate a biosynthesis of vesicles with higher secretory quanta.

Rats were injected with a large dose of reserpine known to stimulate the adrenal medulla. Various times after drug treatment the mRNA levels of several constituents of large dense-core vesicles were determined by northern blot analysis and in situ hybridization. The latter method allowed detection of changes in mRNA levels not only in chromaffin cells, but also in the ganglion cells found in adrenal medulla. Levels of the mRNAs of secretory components of large dense-core vesicles (chromogranins A and B, secretogranin II, VGF, and neuropeptide Y) increased in chromaffin cells by 215-857% after 1-3 days of drug treatment. For partly membrane-bound components (dopamine beta-hydroxylase, prohormone convertase 2, carboxypeptidase H, and peptidylglycine alpha-amidating monooxygenase) the changes ranged from 182 to 315%, whereas for glycoprotein III and for intrinsic membrane proteins (cytochrome b561 and vesicle monoamine transporter 2) no change occurred. In ganglion cells the mRNAs that could be detected for VGF, neuropeptide Y, secretogranin II, carboxypeptidase H, and vesicle monoamine transporter 1 showed an analogous pattern of change, with significant increases for the secretory proteins and no change for the membrane components. From these and previous results we suggest the following concept: Long-lasting stimulation of chromaffin cells or neurons does not induce the biosynthesis of a larger number of vesicles but rather leads to the formation of vesicles containing higher secretory quanta of chromogranins and neuropeptides.

Adrenal Glands↗
PubMed1975

Reserpine and breast cancer in a retirement community.

In an attempt to confirm three reports suggesting a causal link between rauwolfia antihypertensive drugs and female breast carcinoma, all cases of such cancer appearing among the residents of an affluent retirement community were compared with controls chosen from a roster of all women in the same community. Most residents use a single care facility, and patterns of hypertension diagnosis, rauwolfia and other drug use, and medical-care-system patronage were abstracted from medical records. The prevalence of recorded rauwolfia use among the controls were 20 per cent, and that of other drug use was correspondingly high. The risk ratio for rauwolfia use was estimated to be 1.2 (95 per cent confidence interval, 0.7 to 2.2). Risk ratios between 1.0 and 2.0 were also found for other drug use and for measures of care-system patronage. These results do not support the hypothesis that reserpine causes breast cancer.

Aged↗
PubMed1973

Immunochemical demonstration of increased accumulation of tyrosine hydroxylase protein in sympathetic ganglia and adrenal medulla elicited by reserpine.

Chronic administration of reserpine to rats increases, in sympathetic ganglia and adrenal medulla, the activity of tyrosine hydroxylase (EC 1.14.3.x), the enzyme catalyzing the rate-limiting step in the biosynthesis of catecholamines. Immunochemical titration of the enzyme in both adrenal gland and innervated superior cervical ganglia demonstrates that enhanced enzyme activity is entirely attributable to accumulation of more specific enzyme protein and not activation of preexistent enzyme molecules.

Adrenal Medulla↗
PubMed1988

Coexistence and gene expression of phenylethanolamine N-methyltransferase, tyrosine hydroxylase, and neuropeptide tyrosine in the rat and bovine adrenal gland: effects of reserpine.

Expression and regulation of the catecholamine-synthesizing enzymes phenylethanolamine N-methyltransferase (PNMTase; S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28) and tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and the coexisting neuropeptide tyrosine (NPY) were studied in rat and bovine adrenal medulla. By using both immunohistochemistry and in situ hybridization, PNMTase- and NPY-positive cells exhibited a close overlap in bovine medulla and were preferentially localized in the outer two-thirds of the medulla. Although TyrOHase and its mRNA were observed in virtually all medullary gland cells, TyrOHase mRNA levels were much higher in the PNMTase- and NPY-positive cells. After administration of the catecholamine-depleting drug reserpine to rats, a brief increase, followed by a dramatic decrease, in the level of PNMTase mRNA was observed in the adrenal medulla. In contrast, mRNA for both TyrOHase and NPY only exhibited an increase, whereby the TyrOHase mRNA peak preceded that of NPY mRNA. Different regulatory mechanisms may thus operate for these three compounds coexisting in the adrenal medulla.

Adrenal Glands↗
PubMed1992

Expression cloning of a reserpine-sensitive vesicular monoamine transporter.

A cDNA for a rat vesicular monoamine transporter, designated MAT, was isolated by expression cloning in a mammalian cell line (CV-1). The cDNA sequence predicts a protein of 515 amino acids with 12 putative membrane-spanning domains. The characteristics of [3H]serotonin accumulation by CV-1 cells expressing the cDNA clone suggested sequestration by an intracellular compartment. In cells permeabilized with digitonin, uptake was ATP dependent with an apparent Km of 1.3 microM. Uptake was abolished by the proton-translocating ionophore carbonylcyanide p-trifluoromethoxyphenylhydrazone and with tri-(n-butyl)tin, an inhibitor of the vacuolar H(+)-ATPase. The rank order of potency to inhibit uptake was reserpine > tetrabenazine > serotonin > dopamine > norepinephrine > epinephrine. Direct comparison of [3H]monoamine uptake indicated that serotonin was the preferred substrate. Photolabeling of membranes prepared from CV-1 cells expressing MAT with 7-azido-8-[125I]iodoketanserin revealed a predominant tetrabenazine-sensitive photolabeled glycoprotein with an apparent molecular mass of approximately 75 kDa. The mRNA that encodes MAT was present specifically in monoamine-containing cells of the locus coeruleus, substantia nigra, and raphe nucleus of rat brain, each of which expresses a unique plasma membrane reuptake transporter. The MAT cDNA clone defines a vesicular monoamine transporter representing a distinct class of neurotransmitter transport molecules.

Affinity Labels↗
PubMed1957

On the concentration of 5-hydroxytryptamine in mammalian enterochromaffin cells and its release by reserpine.

The enterochromaffin cells of the guinea pig duodenum and 5-hydroxytryptamine incorporated into gelatin models gave, after formalin fixation, nearly identical reactions with methenamine silver, ferric-ferricyanide, and diazotized o-aminoazotoluene. Following formaldehyde fixation the indole reaction with p-dimethylaminobenzaldehyde was negative in tissue enterochromaffin cells; similarly the indole reaction was negative after formaldehyde fixation of gelatin models. In the duodenum of the guinea pig 5-hydroxytryptamine appears to be largely, if not entirely, contained in the enterochromaffin cells. Its intracellular concentration estimated from relative cell volume and assay of concentration in the whole tissue, was not less than 5 mg./gm. of cells, and as judged by the intensity of staining reaction may have been as high as 10 to 20 mg./gm. of cells. Reserpine administered parenterally caused release of the chromogenic material of duodenal enterochromaffin cells and a parallel reduction in the amount of extractable 5-hydroxytryptamine.

Animals↗
PubMed1982

Normothermic ischaemic cardiac arrest of isolated working rat heart: effects of reserpine and propranolol on functional, metabolic and morphological recovery.

The ability to preserve myocardial structural and functional integrity during extended periods of total ischaemia has practical clinical significance. The role of endogenous catecholamines in the onset of irreversible damage in global ischaemia of the isolated rat heart was assessed by beta-blockade or catecholamine depletion. The effects of propranolol and reserpine pretreatment on myocardial ultrastructure, function and metabolism were studied during normothermic ischaemic arrest (NICA) and reperfusion of the isolated working rat heart. beta-Blockade as well as catecholamine depletion resulted in an increase in the percentage of totally ischaemic hearts which recovered mechanically upon reperfusion. In these studies mechanical recovery during reperfusion was associated with reversal of ultrastructural ischaemic alterations, but without an improvement in mitochondrial function. These findings support the concept that failure of mitochondria to recover functionally upon reperfusion is not the cause of either irreversible mechanical failure or ultrastructural damage of the ischaemic myocardium.

Animals↗
PubMed1998

The effect of reserpine, an inhibitor of multidrug efflux pumps, on the in-vitro activities of ciprofloxacin, sparfloxacin and moxifloxacin against clinical isolates of Staphylococcus aureus.

In Staphylococcus aureus, in addition to mutations in the grl and gyr gene loci, multidrug efflux pumps like NorA contribute to decreased fluoroquinolone susceptibility. Efflux pumps can be inhibited by the plant alkaloid reserpine, which, at 20 mg/L, reduced sparfloxacin, moxifloxacin and ciprofloxacin IC50s and MICs by up to four-fold in 11, 21 and 48 of the 102 unrelated clinical isolates tested, respectively. The effect was less pronounced with the hydrophobic drugs sparfloxacin and moxifloxacin than with the hydrophilic drug ciprofloxacin and was stable in all 25 clonally related isolates tested.

Anti-Infective Agents↗
PubMedDate not supplied

LC/MS determination of bromazepam, clopenthixol, and reserpine in serum of a non-fatal case of intoxication.

Combined liquid chromatography and mass spectrometry (LC/MS) with a moving belt interface can be used as a rapid method for the determination of bromazepam, clopenthixol, and reserpine in serum samples obtained from cases of acute overdoses with combinations of these drugs. Low resolution detection limits are about 100 pg for the three drugs, while in high resolution mode the detection limit for bromazepam is shown to be at least 35 pg. Accurate masses were obtained in a serum sample within 5 ppm using high voltage scanning over a narrow mass range for about 10 ng of bromazepam and clopenthixol, respectively. Chemical deactivation of the belt was shown to effectively reduce memory effects and to improve the desorption characteristics of the belt leading to higher yields of evaporated intact molecules.

Anti-Anxiety Agents↗
PubMed1979

The effects of reserpine on microcirculatory flow in rat flaps.

A model flap was developed in the rat which allowed us to quantitate microcirculatory blood flow within a flap, and to correlate the flow with the length of flap eventually surviving. A critical flow of 0.02 and 0.03 ml/min/gm (measured during the first 24 hours after flap elevation by radioactive microspheres) appears to be necessary for tissue survival. Reserpine, in a dose of 5 mg/kg, did not increase blood flow in the flap or the length of flap surviving in this model.

Animals↗
PubMed1976

Effects of reserpine, epidermal growth factor, and cyclic nucleotide modulators on epidermal mitosis.

The mouse ear G2 mitosis assay was modified for the screening of potential antimitotic agents. An inhibitory adrenergic influence, which maintains mitotic rate at a normally low level, was removed by pretreatment of mice with reserpine. This depletes endogenous catecholamines, produces a state of enhanced mitotic activity, and makes the epidermal cells particularly sensitive to mitotic inhibition by agents which elevate the levels of cyclic AMP. Isoproterenol [IC 50 approximately 1 X 10(-9) M], prostaglandins, dibutyryl cyclic AMP [IC 50 approximately 2 X 10(-5) M], papaverine, theophylline and 5' AMP were inhibitory in the assay, whereas dibutyryl cyclic GMP and the cholinergic stimulator carbamylcholine either stimulated or had no effect on mitosis. Epidermal growth factor was employed as an alternate means of stimulating cell division. Skin fron newborn mice or rats pretreated with this substance had increased epidermal mitotic activity which was inhibited cyclic AMP elevators.

Animals↗
PubMed1990

The effect of reserpine, desipramine and thyroid hormone on alpha 1a- and alpha 1b-adrenoceptor binding sites: evidence for a subtype-specific regulation.

Using radioligand binding techniques we studied whether alpha 1a- and alpha 1b-adrenoceptor recognition sites can be regulated independently by drugs and hormones. In rat cerebral cortex subchronic treatment with reserpine enhanced the number of [3H]-prazosin binding sites and the proportion of alpha 1b binding sites. Desipramine treatment which did not alter Bmax values, increased the proportion of alpha 1a and decreased alpha 1b binding sites. In rat myocardium hypothyroidism decreased alpha 1b-adrenoceptor binding sites. These results suggest that alpha 1-adrenoceptors are regulated in a subtype-selective manner.

Animals↗
PubMed1985

Elevation of RNA coding for tyrosine hydroxylase in rat adrenal gland by reserpine treatment and exposure to cold.

When rats are treated daily with reserpine or maintained at 4 degrees C, the level of a specific RNA coding for tyrosine hydroxylase is elevated in the adrenal gland. The increase in this specific RNA temporally precedes and is quantitatively equal to the increase in adrenal tyrosine hydroxylase enzyme activity elicited by these treatments. These results suggest that prolonged stress may lead to changes in the levels of specific RNA species in the adrenal gland.

Adrenal Glands↗
PubMed1959

The effects of reserpine and other agents upon leptazol convulsions in mice.

Reserpine and tetrabenazine reduced the survival time of mice infused with leptazol. This effect was antagonized by pretreatment with iproniazid. The survival time of iproniazid-treated mice was prolonged by 5-hydroxytryptophan but not by 3:4-dihydroxyphenylalanine. These findings suggest a relation between leptazol sensitivity and brain levels of 5-hydroxytryptamine.

5-Hydroxytryptophan↗
PubMed1961

The reserpine-treated cat.

In cats, 24 hr after the administration of 1 mg/kg of reserpine, it was found that (a) the heart is in failure; (b) the sensitivity of the peripheral vessels to adrenaline, noradrenaline and isoprenaline, administered intravenously or close-arterially, is decreased; (c) any blood pressure changes are, as a rule, secondary to changes in heart contraction; and (d) the peripheral blood flow passively follows the blood pressure changes. Furthermore, any improvement of the circulation at this stage was found to be almost exclusively the result of an amelioration in the force of cardiac contraction.

Animals↗
PubMed1969

The effects of phenobarbitone, leptazol, dexamphetamine, iproniazid, imipramine, LSD, chlorpromazine, reserpine and hydroxyzine on the in vivo levels of adenine nucleotides and phosphocreatine in the rat brain.

1. Enzymic and ion-exchange chromatographic analyses were used to measure adenosine triphosphate (ATP), diphosphate (ADP) and monophosphate (AMP) in brain extracts from rats treated with a wide range of centrally acting drugs. Phosphocreatine (PC) was assayed by the acid molybdate method.2. An anaesthetic dose of phenobarbitone caused an increase in brain levels of ATP and PC, and a reduction in ADP and AMP. A convulsant dose of leptazol gave rise to precisely opposite effects. Subanaesthetic (hypnotic) and subconvulsive doses of the two drugs, respectively, produced no alterations in brain nucleotide levels.3. Among the psychotropic drugs, dexamphetamine, LSD and hydroxyzine, at the doses used, caused no changes in brain levels of the adenine nucleotides. Iproniazid and imipramine caused slight increases in the ATP level and ATP / ADP ratio, respectively. Chlorpromazine failed to give rise to any effect in the nucleotides 3 hr after administration, but produced a rise in brain ATP after 6 hr. Reserpine, on the other hand, caused a fall in the ATP/ADP ratio 6 hr after injection.4. These results indicate that some psychotropic drugs can cause small changes in the rat brain ATP/ADP ratio but do not support claims by certain workers that such changes correlate closely with the behavioural effects of these drugs.

Adenine Nucleotides↗