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S Finkielman

Publications and source records attributed to S Finkielman.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1988

Serotonin and melatonin synthesis in peripheral blood mononuclear cells: stimulation by interferon-gamma as part of an immunomodulatory pathway.

Serotonin and melatonin inhibit phytohemagglutinin- (PHA) induced interferon-gamma (IFN-gamma) production by lymphocytes. In this paper, it is shown that IFN-gamma-increased tryptophan uptake by lymphocytes and macrophages led to an enhanced production of serotonin. When IFN-gamma and serotonin were added together to a lymphocyte culture, N-acetyl serotonin and melatonin production was increased, whereas the path to 5-hydroxy-indoleacetic acid remained unchanged. Therefore, the stimulated IFN-gamma production of serotonin and melatonin by lymphocytes and macrophages and the inhibition of IFN-gamma synthesis by these indoleamines suggest a hypothesis for an immunoregulatory circuit.

Cells, Cultured↗
PubMed1988

Differential release of enkephalin and enkephalin-containing peptides from perfused cat adrenal glands.

We have compared the enkephalin-like material derived from proenkephalin released from perfused cat adrenal glands stimulated with pilocarpine (5 X 10(-4)M) and nicotine (5 X 10(-6) M). In addition, two doses of acetylcholine (10(-5) and 10(-4) M) and 50 mM K+ were tested. Free Met-enkephalin immunoreactivity and total Met-enkephalin immunoreactivity, as determined by enzymatic digestion of large enkephalin-containing fragments, were coreleased with catecholamines. Free Met-enkephalin immunoreactivity represented 13% of total immunoreactivity for nicotinic stimulation, 46% for pilocarpine, 33% for 10(-5) M acetylcholine, 22% for 10(-4) M acetylcholine, and 16% for 50 mM K+. Analysis of the perfusate by gel filtration showed that 80% of the total Met-enkephalin immunoreactivity whose release was induced by pilocarpine was eluted in fractions corresponding to fragments of low molecular weight, whereas these fractions accounted only for 10% of the total Met-enkephalin immunoreactivity whose release was induced by nicotine. HPLC analysis of low-molecular-weight peptide fractions revealed that Met-enkephalin, Met-enkephalin-Arg-Gly-Leu, and Met-enkephalin-Arg-Phe represented 69% of total Met-enkephalin immunoreactivity whose release was induced by pilocarpine. These results indicate that selective activation of muscarinic receptors is followed by release of low-molecular-weight material, whereas nicotine application also yielded high-molecular-weight peptides. Furthermore, increasing the acetylcholine concentration from 10(-5) to 10(-4) M and using 50 mM K+ increased proportionally the high-molecular-weight peptide secretion. Results are discussed in relation to the existence of a heterogeneous population of granules either in the same cell or in different cells, containing proenkephalin-derived peptides. (ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1988

Adrenal proenkephalin-derived peptides during postnatal development in spontaneously hypertensive rats.

Adrenal enkephalin and enkephalin-containing peptides were studied during postnatal development in normotensive (WKY) and spontaneously hypertensive rats (SHR). The effect of chronic treatment with the ganglionic blocker chlorisondamine (5 mg/kg) was also assessed. Free enkephalin immunoreactivity and total enkephalin immunoreactivity, as determined by enzymatic digestion of large enkephalin containing fragments, were quantitated in the adrenal glands at 11 days and 7, 16, and 24 weeks of age. Both total and free metenkephalin were significantly diminished in the adrenal of SHR when compared to WKY at all ages tested. The analysis of the chromatographic profile showed that SHR displayed reduced levels of high and low molecular weight materials at 11 days and 16 weeks of age; however intermediate compounds were high in the glands of these animals. Similar increased values for free met-enkephalin were found in adrenals of WKY and SHR after ganglionic blocker treatment, which means that the relative increase was larger in SHR than WKY; while for total enkephalin the relative increase and the concentration reached in SHR was about half of those presented in WKY. These and other results presented suggest that the basic alteration of the adrenal proenkephalin system of SHR may be due to a genetic reduction of proenkephalin levels. Otherwise, the free enkephalin decrease could be related to changes in nervous input to the adrenal gland.

Adrenal Glands↗
PubMed1988

Low TRH-TSH responses in human essential hypertension.

Thirty female and male essential hypertensive patients and eighteen normotensive controls were submitted to the TRH-TSH conventional test (200 ug intravenously, bolus injection of TRH). Supramaximal doses of 400 and 600 ug were repeated with a week interval to each subject. Hypertensives showed a significant lower response to both conventional and supramaximal TRH doses. Hypothalamic-pituitary-thyroid axis abnormalities, secondary to TRH-receptor alterations, could account for this result.

Adult↗
PubMed1988

Angiotensin converting enzyme activity in the amygdaloid complex in a neurogenic hypertensive model.

The bilateral destruction of the ventral noradrenergic pathway induced by 6-hydroxydopamine (6-OHDA) administration into the ventral pons led to an increase in arterial blood pressure (ABP) and norepinephrine depletion in the amygdaloid complex, nucleus accumbens, septal area and olfactory bulb. Specific angiotensin converting enzyme (ACE) activity was significantly increased only in the amygdaloid complex (Control: 4.56 +/- 0.95; Vehicle: 4.08 +/- 1.07; 6-OHDA: 11.76 +/- 1.84). A significant correlation between arterial blood pressure and specific ACE activity levels in the amygdaloid complex was observed (r: 0.775; p less than 0.002). These results suggest that an increase in specific ACE activity of the amygdaloid complex after norepinephrine depletion could play a role in the development of hypertension in this model.

Amygdala↗
PubMed1987

Serotonin mediates cardiovascular responses to acetylcholine, bradykinin, angiotensin II and norepinephrine in the lateral septal area of the rat brain.

The infusion of acetylcholine, bradykinin, angiotensin II, norepinephrine and serotonin into the lateral septal area produced a dose-dependent increase of arterial blood pressure and heart rate. A pattern of inhibition of these cardiovascular responses, produced by pretreatment of the lateral septal area with phentolamine, 6-hydroxydopamine, methysergide and 5,7-dihydroxytryptamine was disclosed. These results suggest that the effects of acetylcholine, bradykinin and partially of angiotensin II, depend on the release of norepinephrine and the actions of this neurotransmitter in turn depend on the integrity of the serotonergic system in the lateral septal area.

5,7-Dihydroxytryptamine↗
PubMed1987

Angiotensin II regulates interferon-gamma production.

An extensive literature links the immune responses to neuroendocrine regulation. We have examined the effects of the neuropeptide hormone angiotensin II on the production of the immunomodulatory lymphokine interferon-gamma (IFN-gamma). Angiotensin II (10(-6)-10(-8) M) stimulated (three- to fivefold) the IFN-gamma production in human blood lymphocytes obtained from normal individuals. At 10(-9) M angiotensin II stimulation disappeared and was reestablished at physiological concentrations of the neuropeptide (10(-10)-10(-11) M). Stimulation by angiotensin II was compared with the classical effect of the lectin phytohemagglutinin, and it was seen that both actions are mediated by external calcium (as they are blocked by EGTA 2.5 mM) and that the stimuli follow different kinetics, reaching the steady state at 6 h with angiotensin II and later (18 h) when the lectin was used. The effect of angiotensin II over the IFN-gamma production was blocked by its analog sarcosine 1-isoleucine 8-angiotensin II, showing the specificity of angiotensin II action. These findings demonstrate a selective biological regulation of IFN-gamma production by angiotensin II and suggest another regulation pathway of immune responses.

Angiotensin II↗
PubMed1986

Interaction between acetylcholine and bradykinin in the lateral septal area of the rat brain: involvement of muscarinic receptors in cardiovascular responses.

The lateral septal area was used as a model to study the interaction between acetylcholine (Ach) and bradykinin on arterial blood pressure, since both mediators are present in this region. In the lateral septal area, the administration of the peptide or Ach produced a long-lasting, sympathetic-mediated increase of arterial blood pressure which was blocked by atropine. Pretreatment of the lateral septal area with hemicholinium-3, which depletes stores of acetylcholine, partially blocked the pressor effect of bradykinin but not that of Ach. Captopril--an inhibitor of kininase II--enhanced the pressor effects of bradykinin and Ach. Synaptosomal studies showed that bradykinin increased sodium-dependent, high-affinity uptake of choline and the conversion of [3H]choline to [3H]acetylcholine. Competition experiments using the highly specific muscarinic antagonist [3H]quinuclidinyl benzilate, demonstrated that bradykinin displaced the muscarinic antagonist from its receptor-ligand complexes. These results suggest that in the lateral septal area acetylcholine and bradykinin interact in a positive feed-back which amplifies pressor responses.

Acetylcholine↗
PubMed1986

Saralasin blocks the effect of angiotensin II and extracellular fluid saline expansion on the Na-K-ATPase inhibitor release in rats.

A low molecular weight substance which behaves like ouabain as inhibitor of brain membrane Na-K-ATPase and 3H-ouabain binding was found in plasma after saline expansion of extracellular fluid or angiotensin II infusion into the third brain ventricle in the rat. Intracerebroventricular infusion of angiotensin II antagonist, saralasin, blocks the increase of the Na-K-ATPase inhibitor produced by infusion of angiotensin II into the third ventricle or extracellular fluid saline expansion.

Angiotensin II↗