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Biomedical subjects

S Finkielman

Publications and source records attributed to S Finkielman.

At least 19 recordsLinked to original sources
PubMed1992

Brain amines in glucocorticoid-induced hypertension in the rat.

A two week administration of the glucocorticoid betametasone to male Wistar rats produced a mild hypertensive state. The brain of these rats showed some significant changes in amine and metabolite content with respect to normotensive controls. Epinephrine and metanephrine were increased in the rostral ventrolateral medulla and in the preoptic area. Epinephrine also increased in the septal area. Normetanephrine decreased in the rostral ventrolateral medulla. Dopamine and homovanillic acid increased in septal and preoptic areas. Dopamine alone increased in rostral ventrolateral medulla. Serotonin and 5-hydroxyindole-3-acetic acid increased in the septal area and dorsal medulla. These changes suggest significant alterations in the aminergic activity of the brain circuitry known to regulate cardiovascular functions; the changes may play a basic role in the development and maintenance of glucocorticoid-induced hypertension.

Animals↗
PubMed1992

The cholinergic system participates in thyrotropin-releasing hormone (TRH) regulation.

The effect of chronic atropine treatment was studied on thyrotropin releasing hormone (TRH) content of several brain areas in Wistar rats. Atropine produced TRH increases in the septal area, preoptic area and the hypophysis; this was observed when rats were killed immediately after the last dose, while a decrease was observed only in the hypophysis 48 h after the last atropine dose. TRH concentration in cerebrospinal fluid rose significantly after atropine withdrawal with respect to controls. Treatment with eserine, an acetylcholinesterase inhibitor, produced the same effect. These results indicate cholinergic participation in central TRH regulation.

Animals↗
PubMed1992

Central bradykininergic system in normotensive and hypertensive rats.

1. The kinin antagonist des-Arg9-[Leu8]bradykinin, injected into the lateral ventricle, caused a long-lasting, dose-dependent reduction in arterial blood pressure and heart rate in spontaneously hypertensive rats but not in normotensive Wistar-Kyoto rats; the antagonist also blocked the pressor response to ventricularly infused bradykinin in both strains. 2. Bradykinin content was increased in the hypothalamus and septum and decreased in the dorsal medulla of spontaneously hypertensive rats when compared with those of normotensive Wistar-Kyoto rats, whereas similar bradykinin contents were observed in the pineal gland, hypophysis and rostroventrolateral medulla of both rat strains. 3. Increased concentrations of bradykinin and its precursor kininogen were found in the cerebrospinal fluid of spontaneously hypertensive rats. 4. Bradykinin receptor numbers, measured as the binding of [125I-Tyr1]bradykinin to nervous tissue, were found to be increased in the dorsal medulla and hypophysis, and to be decreased in the pineal gland, of spontaneously hypertensive rats. 5. Therefore, the central kinin system may participate, by both pre- and post-synaptic mechanisms, in the maintenance of hypertension in spontaneously hypertensive rats.

Animals↗
PubMed1992

Early complete maturation of proenkephalin processing induced by dexamethasone in the adrenal gland of neonatal rats.

We have previously found that proenkephalin processing is incomplete in the neonatal rat adrenal medulla and have postulated that immaturity of either the nervous input to the gland or the endocrine hypothalamus-pituitary-adrenal axis might be involved in the failure of the gland to yield free met-enkephalin. Therefore, we investigated whether cholinergic and glucocorticoid agonists may act in vivo on neonatal proenkephalin processing; reserpine, a strong activator of precursor cleavage, was also tested. Acute administration of nicotine, pilocarpine and reserpine to 24-hour-old rats increased the content of enkephalin-containing peptides (ECP) after 72 h (4-day-old rats) and activated the posttranslational processing of proenkephalin to high, intermediate and low molecular weight peptides respectively, although free met-enkephalin was not produced. Chronic treatment with nicotine and pilocarpine neither modified the concentration of ECP nor were able to induce free metenkephalin production. Chronic administration of dexamethasone increased ECP levels in the adrenal of 4-day-old rats and caused proenkephalin processing to intermediate- and low-molecular-weight products including the production of free met-enkephalin. These results indicate that only dexamethasone was able to induce the production of met-enkephalin in the adrenal of neonatal rats, suggesting an involvement of the hypothalamus-pituitary-adrenal axis in the proteolytic maturation of proenkephalin during the ontogeny of rat adrenal medulla.

Adrenal Glands↗
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↗
PubMed1992

The inhibitory effect of the muscarinic agonist pilocarpine on lymphocyte activation involves the IL-2 pathway and the increase in suppressor cell function.

The inhibition of lymphocyte DNA synthesis by the cholinergic muscarinic agonist pilocarpine (5 x 10(-4) M) was not reversed by addition of exogenous recombinant Interleukin-2 (100-1000 IU/ml). Pilocarpine did not inhibit Interleukin-2 (IL-2) production by human peripheral blood mononuclear cells but decreased the number of interleukin-2 receptor bearing cells (TAC positive cells). Furthermore, pilocarpine increased the CD8:CD4 T lymphocyte ratio enhancing the suppressor cell function. All these effects were blocked by the muscarinic antagonist atropine (1 x 10(-6) M). As described for the specific lymphocyte nicotinic stimulation, the pure cholinergic muscarinic stimulation inhibits lymphocyte proliferation by enhancing suppressor activity.

Brain↗
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

Glucocorticoid-induced hypertension in rats: role of the central muscarinic cholinergic system.

Betamethasone was administered on alternate days to rats, and the role of the central cholinergic system in the development of hypertension assessed. After 15 days of treatment the systolic blood pressure of treated rats was significantly higher than that of control rats. Peripheral administration of atropine but not of methyl atropine reduced systolic pressure in glucocorticoid-treated rats and had no effect in controls. Therefore, [3H]quinuclidinyl benzylate binding, sodium-dependent high-affinity choline uptake and choline acetyltransferase studies were performed in the septal area, anteroventrolateral medulla (AVLM), anterior hypothalamic preoptic area (AH/PO) and hypothalamus. The density of muscarinic receptors was increased in the hypothalamus and AVLM of treated rats without significant changes in affinity. Choline acetyltransferase activity significantly decreased in the AVLM and increased in the AH/PO. In addition, a decrease in the hypothalamus and an increase in the AH/PO of sodium-dependent high-affinity choline uptake was observed in glucocorticoid-treated rats. These results suggest the presence of an enhanced muscarinic cholinergic activity in several brain nuclei in rats with glucocorticoid-induced hypertension. This activation could be due to pre- and post-synaptic hypersensitivity.

Animals↗
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

Proenkephalin system in human polymorphonuclear cells. Production and release of a novel 1.0-kD peptide derived from synenkephalin.

In the hematopoietic system a pluripotent stem cell generates precursors for lymphoid and myeloid lineages. Proenkephalin-derived peptides were previously detected in differentiated lymphoid cells. We have studied whether the proenkephalin system is expressed in a typical differentiated cell of the myeloid lineage, the neutrophil. Human peripheral polymorphonuclear cells contain and release proenkephalin-derived peptides. The opioid portion of proenkephalin (met-enkephalin-containing peptides) was incompletely processed, resulting in the absence of low molecular weight products. The nonopioid synenkephalin (proenkephalin 1-70) molecule was completely processed to a 1.0-kD peptide derived from the COOH-terminal. This molecule was characterized in neutrophils by biochemical and immunocytochemical methods. The chemotactic peptide FMLP and the calcium ionophore A23187 induced the release of the proenkephalin-derived peptides, and this effect was potentiated by cytochalasin B. The materials secreted were similar to those present in the cell, although in the supernatant a higher proportion corresponded to more processed products. The 1.0-kD peptide was detected in human, bovine, and rat neutrophils, but the chromatographic pattern of synenkephalin-derived peptides suggests a differential posttranslational processing among species. These findings demonstrate the existence of the proenkephalin system in human neutrophils and the production and release of a novel 1.0-kD peptide derived from the synenkephalin molecule. The presence of opioid peptides in neutrophils suggests their participation in the inflammatory process, including a local analgesic effect.

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↗