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Biomedical subjects

V E Nahmod

Publications and source records attributed to V E Nahmod.

At least 37 records · Page 2Linked to original sources
PubMed1992

Interaction between thyrotrophin-releasing hormone and the muscarinic cholinergic system in rat brain.

TRH increases the pressor response to acetylcholine through an increment in muscarinic receptors. As chronic atropinization produces a similar effect, we hypothesized that both phenomena may be related. The effect of chronic atropine treatment on the TRH content of several brain areas in Wistar rats was studied. Atropine produced significant increases in TRH content in the preoptic and septal areas, while decreases were observed in the hypothalamus and hypophysis. The concentration of TRH in cerebrospinal fluid rose significantly in atropine-treated rats compared with controls. A similar effect was observed with eserine, an acetylcholinesterase inhibitor. Finally, perfusion of brain preoptic area slices from normal rats with Krebs-Ringer solution in the presence of pilocarpine increased basal TRH release significantly and this effect was blocked by atropine. These results are compatible with a muscarinic control on the activity of the central TRH system.

Animals↗
PubMed1991

Melatonin biosynthesis and metabolism in peripheral blood mononuclear leucocytes.

Cultured human peripheral blood mononuclear leucocytes (PBML) were able to synthesize indoleamines, including melatonin, and were also able to convert melatonin taken up from the incubation medium into N-acetyl-5-hydroxytryptamine (NAHT) and 5-hydroxytryptamine (5-HT). These compounds were analysed by h.p.l.c., and melatonin was additionally characterized by two-dimensional t.l.c., mass spectrometry and radioimmunoassay. Only hydroxyindoles were detected by h.p.l.c. in unstimulated PBML culture. Sustained stimulation by melatonin or interferon-gamma (IFN-gamma) increased markedly the basal production of 5-HT. IFN-gamma- or 5-HT-stimulated (but not resting) cells produced NAHT and melatonin. Furthermore, the addition of melatonin to the culture medium strongly enhanced NAHT and 5-HT production without affecting tryptophan hydroxylation, suggesting the possibility of direct or indirect transformation of melatonin into NAHT and 5-HT.

Cells, Cultured↗
PubMed1991

Lesions of the medial septal nucleus produce a long-lasting inhibition of T lymphocyte proliferation.

The influence of the central cholinergic system on the immune system was studied in Wistar rats by lesioning the medial septal nucleus. This lesion inhibited T cell proliferation of splenocytes and thymocytes induced by the mitogens concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM) up to 25 days and did not affect proliferation at 40 days after lesioning. In contrast, the response to the B cell mitogen lipopolysaccharide from E. coli (LPS) was not affected at any time. These findings suggest a regulatory role of the cholinergic medial septal nucleus on T lymphocyte proliferation.

Animals↗
PubMed1991

Serotonin inhibition of tumor necrosis factor-alpha synthesis by human monocytes.

Serotonin inhibited in a concentration dependent way (10(-3) M to 10(-10) M) the LPS induced Tumor Necrosis Factor-alpha synthesis both, when added to the monocyte cultures from the beginning and when added together with the activating stimulus 8 hours before the end of the culture. The inhibitory effect was specifically blocked by the 5-HT1 and 5-HT2 serotonin antagonist methysergide and the 5-HT2 receptor antagonist ketanserin. This indicates that only the 5-HT2 receptor family (5-HT2 or 5-HT1C) may be involved in the inhibitory effect. Serotonin seems to play an important immunomodulatory role in macrophage functions.

Humans↗
PubMed1991

Cholinergic hyperactivity in the lateral septal area of spontaneously hypertensive rats: depressor effect of hemicholinium-3 and pirenzepine.

In the lateral septal area of spontaneously hypertensive rats, but not in Wistar-Kyoto rats, the selective M1 antagonist, pirenzepine, and the depletion of acetylcholine storage, by hemicholinium-3 (HC-3), decreased blood pressure. The selective M1 agonist McNeil-A-343, produced a pressor response only after treatment of the lateral septal area with HC-3 in spontaneously hypertensive rats. Carbachol, at doses that mainly affect M2 muscarinic receptors, caused no cardiovascular changes in either strain, pointing to the main intervention of the M1 subtype of muscarinic receptor in the hypertensive condition. In addition, increases in the density of binding sites for [3H]QNB and in Vmax of sodium-dependent, HC-3-inhibitable, high affinity uptake of choline were demonstrated, without significant changes of the activity of choline acetyltransferase in the lateral septal area of spontaneously hypertensive rats. These results suggest that a hyperactivity of the cholinergic system of this area could play a role in the development and/or maintenance of hypertension in spontaneously hypertensive rats.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1991

Release of acetylcholine from isolated canine renal tissue.

Slices of canine kidney were incubated with [3H]choline and Ringer-Krebs solution for 30 min. Secretion of [3H]acetylcholine ([3H]ACh) was evoked by either 1) an electrical field stimulation (0.5-1 Hz, 2 ms, 20 V) or 2) high-potassium (57 mM) superfusion for 3 min to depolarize nerve terminals. With these stimulatory schedules, the 3H release mainly consists of [3H]-ACh. The ACh release is Ca2+ dependent and blocked in presence of a Mg2(+)-rich medium. Thus suppression of ongoing neuronal activity by tetrodotoxin and blockade of nicotinic receptors by hexamethonium reduced the electrically evoked ACh release. With both stimulatory procedures, the secretory response was modified by pilocarpine and atropine. In addition, the release of [3H]ACh produced by electrical field stimulation was inhibited by neostigmine, indicating the presence of functional presynaptic receptors in cholinergic putative terminals. Activation of these receptors depresses ACh secretion. The disruption of extrinsic renal nerves 7 days before did not diminish [3H]ACh release caused by K+ stimulation and, conversely, increased [3H]ACh released by electrical field stimulation. These data support the presumed existence of cholinergic nerve terminals in the canine kidney that can release ACh under suitable conditions of stimulation.

Acetylcholine↗
PubMed1991

Effects of sodium o-iodobenzoate on acid-base parameters and survival in dogs with hemorrhagic shock.

Sodium o-iodobenzoate (OISB) produces an increase in P50 (PO2 at 50% of oxyhemoglobin saturation) and survival when infused at the time of initiation of prolonged hemorrhagic shock in dogs. Acid-base parameters improved during treatment, and plasma lactic acid concentrations showed smaller rises than in nontreated control animals. Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) rose in prolonged hemorrhagic shock in the control group and conversely decreased in OISB-treated dogs. OISB did not require red cell integrity, since its effects were still more marked in hemolyzed blood. The therapeutic benefit of OISB, appears to be related to a direct effect of the agent on the hemoglobin molecule.

2,3-Diphosphoglycerate↗
PubMed1990

Pineal hyperactivity in spontaneously hypertensive rats: muscarinic regulation of indole metabolism.

1. Choline acetyltransferase activity and [3H]quinuclidinyl benzylate-binding sites were detected in the pineal gland of normotensive Wistar-Kyoto rats and of spontaneously hypertensive rats. 2. In vitro, muscarinic activation by pilocarpine increased the pineal metabolic production of hydroxyindole derivatives up to 5-hydroxytryptamine and produced a less marked stimulation of melatonin biosynthesis. 3. Electrical field stimulation of pineal gland slices caused similar metabolic effects. 4. Muscarinic blockade with atropine inhibited the effects on hydroxyindole metabolism. 5. [3H]Quinuclidinyl benzylate-binding sites, indicative of muscarinic receptors, were more numerous, and basal 5-hydroxytryptamine and melatonin levels were higher, in the pineal gland of spontaneously hypertensive rats compared with Wistar-Kyoto rats. 6. The atropine-sensitive metabolic effects of pilocarpine and electrical field stimulation on the pineal gland were increased in spontaneously hypertensive rats compared with Wistar-Kyoto rats.

Animals↗
PubMed1990

Differential association of endogenous proenkephalin-derived peptides with membranes of microsomes from rat striatum, adrenal medulla and heart ventricle.

Proenkephalin-derived peptides, in common with other prohormones, are associated with membranes of microsomes and secretory granules in the bovine adrenal medulla. Post-translational processing of the precursor molecule varies depending upon the tissue. The relationship between post-translational events in different tissues was examined by studying the membrane association of endogenous proenkephalin-derived peptides in the crude microsomal fraction of rat adrenal medulla, brain striatum and heart ventricle. [Met]-Enkephalin and synenkephalin (proenkephalin(1-70)) immunoreactivities were quantified by radioimmunoassay after sequential enzymatic digestion with trypsin and carboxypeptidase B. Between 60 and 75% of total immunoreactive peptides present in intact microsomes of the three tissues were associated with membranes and specifically released with 2 M KSCN (pH 7.4). Analysis of the chromatographic profile of materials present in the soluble and associated fractions produced the following results. In the three tissues the materials associated with microsomal membranes corresponded to peptides larger than 3-5 kDa and displayed synenkephalin and [Met]-enkephalin immunoreactivity. Adrenal and heart microsomes showed a continuous pattern of membrane-associated proenkephalin-derived peptides of high, intermediate and low molecular weights containing the synenkephalin and [Met]-enkephalin sequences. These tissues, however, presented quantitative differences, as the highest concentrations belonged to materials larger and smaller than 12.5 kDa in adrenal and heart microsomes respectively. On the other hand, brain striatal microsomes displayed a discontinuous pattern of associated materials, with the absence of some products of high and intermediate molecular weight. Only in the soluble fraction of striatal microsomes were peptides detected of high and intermediate molecular weight containing the [Met]-enkephalin but not the synenkephalin sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1990

Interaction of angiotensin II with the cholinergic and noradrenergic systems in the rat pineal gland: regulation of indole metabolism.

The pineal gland, angiotensin, and noradrenergic and cholinergic systems are involved in the regulation of tissue indole metabolism. Angiotensin II increased noradrenaline release and the production of hydroxy- and methoxyindoles by pineal slices. Electrical field stimulation (EFS) of pineal slices released angiotensin II and reproduced many of the actions of exogenous angiotensin II on serotonin and melatonin biosynthesis and release. Both sarcosine-isoleucine-angiotensin II ([Sar, Ile]-ANG II) and atropine blocked, and nadolol increased, the effect of EFS and exogenous angiotensin II on serotonin production. Nadolol blocked both the EFS-induced and the angiotensin II-induced production of melatonin. Atropine and [Sar, Ile]-ANG II did not modify melatonin biosynthesis in electrically stimulated slices, but the muscarinic receptor antagonist increased the stimulatory effect of angiotensin II. These data showed that EFS released angiotensin II and noradrenaline from pineal slices and that a close functional connection exists between the peptide and acetylcholine. The stimulation of serotonin biosynthesis and release by these two neurotransmitters was negatively regulated by noradrenaline acting through beta-adrenergic receptors.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1989

Mitogenic activation of the human lymphocytes induce the release of proenkephalin derived peptides.

Several reports indicate that enkephalins participate in lymphocyte proliferation and several events of the immune response. It has been proposed that peptides involved in these processes may originate in the nervous system or endocrine glands. We have found that human peripheral blood lymphocytes (PBL) activated with a mitogenic agent contain and release proenkephalin derived peptides. The kinetics of met-enkephalin and cryptic products of proenkephalin in PBL activated with phytohemaglutinin (PHA) were studied. Peptides were released to the supernatant of stimulated PBL, reaching the highest values after 18 to 24 hours. The material secreted corresponds to high, intermediate and low molecular weight peptides derived from proenkephalin, displaying met-enkephalin and synenkephalin (proenkephalin 1-70) immunoreactivity. Therefore, an intrinsic lymphocytic proenkephalin system is induced by PHA and may play an important role in the regulation of the immune response.

Adult↗
PubMed1989

The muscarinic agonist pilocarpine inhibits DNA and interferon-gamma synthesis in peripheral blood mononuclear cells.

Lymphocyte basal DNA synthesis and proliferative responses to phytohemagglutinin (PHA) showed a dose-dependent (5 X 10(-5)-5 X 10(-3) M) inhibition by the muscarinic agonist pilocarpine, in contrast to the basal enhancing effect produced by the M2 muscarinic-nicotinic agonist carbachol. The effect of pilocarpine was reversed by both atropine (1 X 10(-6) M) and pirenzepine (1 X 10(-7)-1 X 10(-8) M), M1-M2 and M1 muscarinic antagonists, respectively. The effect of pilocarpine may thus be specific for the M1 muscarinic receptor. Pilocarpine also inhibited interferon-gamma (IFN-gamma)-PHA induced production, but was unable to reverse the pokeweed mitogen (PWM)-induced DNA synthesis. Distinct immunoregulatory activities are suggested for cholinergic muscarinic receptors M1 and M2.

Cells, Cultured↗
PubMed1989

Evidence for cholinergic innervation in dog renal tissue.

Denervation procedures that affect the sympathetic system of the kidney, as demonstrated by norepinephrine depletion of renal tissue, increased urine volume, fractional sodium excretion, and free water clearance in anesthetized water-loaded dogs. These increases were reduced by atropine, which also blocked the increase above those basal functional levels produced by acetylcholine in both innervated and denervated kidneys. An in vitro tubular cell preparation of innervated kidneys corresponding to the outer cortex showed [3H]quinuclidinyl benzilate (QNB) binding parameters characteristic of muscarinic receptors. Denervation did not change either [3H]QNB binding parameters or the ability of inner and outer cortex cells to perform the hemicholinium-3-inhibitable, sodium-dependent choline uptake and conversion of [3H]choline to [3H]acetylcholine. This cell membrane behavior is similar to that observed in tissues where cholinergic neuronal structures are present, suggesting the existence of a cholinergic innervation of the kidney, independent of the integrity of vessel-traveling nerves. Similarly, the finding of choline acetyltransferase in renal tissue, unaffected by sympathetic denervation, seems to confirm the presence of cholinergic nerve terminals. The cholinergic system may thus contribute to the regulation of tubular reabsorption of sodium and water in some conditions.

Acetylcholine↗
PubMed1989

Muscarinic effects on the hydroxy- and methoxyindole pathway in the rat pineal gland.

[3H]Quinuclidinyl benzylate ([3H]QNB)-binding sites, showing similar properties to cholinergic muscarinic receptors in other tissues, were disclosed in the rat pineal gland. Functionality of these receptors was demonstrated, as in-vitro muscarinic activation by pilocarpine increased the pineal metabolic production of the hydroxyindole derivatives 5-hydroxytryptophan and serotonin, with a slight effect on melatonin biosynthesis. Electric-field stimulation of pineal slices caused similar metabolic effects. These effects were inhibited by muscarinic blockade with atropine and enhanced by neostigmine inactivation of acetylcholinesterase. These results suggest that acetylcholine is the neurotransmitter involved. Cholinergic activity may, therefore, regulate indole metabolism in the pineal gland.

Animals↗
PubMed1989

Ketanserin in the treatment of essential hypertension. A double blind trial against metoprolol followed by one-year open treatment.

The present study was designed to compare the antihypertensive potencies of ketanserin and metoprolol in a double-blind trial and to study ketanserin long-term efficacy in a one-year open trial, plain or combined with metoprolol, according to diastolic blood pressure (DBP) normalization. Thirty-four patients were randomly assigned to two groups, one (n = 17) received ketanserin, 80 mg/day, and the other, (n = 17) metoprolol, 200 mg/day. After 3 mo. double blind treatment, all patients received plain ketanserin, or combined with metoprolol if ketanserin failed to normalize DBP. A significant effect was demonstrated after 3 mo. double blind treatment, for both drugs, in both standing and supine DBP (p less than 0.001). In the one-year follow-up, all patients received ketanserin and were divided in: I (n = 15) previously treated with the same drug; II (n = 2) plus metoprolol, in whom ketanserin had failed to decrease DBP; and III (n = 15) previously treated with metoprolol. In group I the blood pressure lowering effect of ketanserin remained constant during the one-year follow-up. In group II a trend in the decrease of parameters was observed. In group III, supine DBP diminished from 92.5 +/- 2 mmHg during treatment with metoprolol to 86.0 +/- 2 at 12 mo., after treatment with ketanserin (p less than 0.05). In groups I and III, 24/30 of patients normalized their DBP during one-year ketanserin open treatment. Ketanserin appears as a new alternative in the treatment of mild and moderate essential hypertension.

Adult↗
PubMed1989

[The central nervous system and neuroendocrine system in the regulation of the immune response].

There is at present a clear trend in the study of psychoneuroimmunoregulatory events. Different experimental models have demonstrated: a) the participation of stress, psychosocial factors and the central nervous system in the regulation of the immune response; b) an extensive innervation by the autonomic nervous system of the lymphatic organs; c) the presence of receptors for the neuroendocrine mediators in the mononuclear peripheral cells; d) the activity of neuropeptides, hormones and neurotransmitters in lymphocyte activation and function; e) the production of neuroendocrine substances by lymphocytes; f) the existence of feedback pathways in the immune system. In our laboratory we have contributed to these studies with the description of: a) the regulatory activity of different neuroendocrine substances on interferon-gamma production; b) the characterization of the immune regulation exercised by the muscarinic cholinergic system; c) the in vitro activity of the indoleamines, serotonin and melatonin on the immune response, and the production of these indoleamines by lymphocytes and monocytes, thus establishing a model of paracrine regulation.

Adrenal Cortex Hormones↗
PubMed1988

Immunomodulation by indoleamines: serotonin and melatonin action on DNA and interferon-gamma synthesis by human peripheral blood mononuclear cells.

Different concentrations of indoleamines, serotonin and melatonin, inhibited phytohemagglutinin stimulated DNA synthesis. Thus, 10(-3) to 10(-4) M of either indoleamine acted at the optimal phytohemagglutinin concentration, while 10(-3) to 10(-7) M acted at suboptimal phytohemagglutinin levels. The serotonin effect was reversed by the serotonergic S1-S2 receptor antagonist methysergide but not by the S2 antagonist ketanserin. This indicates that only the S1 receptor is involved in the inhibitory effect. Inhibition of lymphoproliferation by indoleamines was also exerted on pokeweed mitogen and protein A from Staphylococcus aureus stimulations. Serotonin and melatonin also inhibited phytohemagglutinin and protein A from Staphylococcus aureus induction of interferon-gamma synthesis. The initial uptake of Ca2+ was not affected by indoleamines, suggesting that it is not the mechanism of their inhibitory effects. As interferon-gamma induced tryptophan uptake by T lymphocyte- and macrophage-depleted populations, and tryptophan is the metabolic precursor of serotonin and melatonin, a new immunoregulatory circuit is postulated.

Calcium↗