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M Wielosz

Publications and source records attributed to M Wielosz.

At least 19 recordsLinked to original sources
PubMed1987

Regulation of beta adrenergic receptors on rat mononuclear leukocytes by stress: receptor redistribution and down-regulation are altered with aging.

In vitro incubation of mononuclear leukocytes (MNL) with catecholamines desensitizes beta adrenergic receptors, meaning isoproterenol-stimulated cyclic AMP accumulation decreases. This desensitization is accompanied by two patterns of receptor changes: first, reduction of surface receptors (defined as binding of [3H]dihydroalprenolol inhibited by 1 microM CGP 12177 [4-3-tertiarybutylamino-2-hydroxypropoxy)-benzimidazole- 2-on-hydrochloride]) without any change in the total number of [3H] dihydroalprenolol binding sites inhibited by 1 microM propranolol (receptor redistribution); then reduction of the total number of receptors (receptor down-regulation). In the present study we investigated receptor redistribution and down-regulation under physiological conditions by raising endogenous catecholamines in the rat by stress. In young rats a single immobilization stress induced MNL beta adrenergic receptor redistribution: the number of surface receptors was reduced by about 50% but the total number remained the same. Receptor redistribution was prevented completely in rats pretreated with beta-blocking nadolol. Repeated stress down-regulated the MNL beta adrenergic receptors as shown by a reduction in the total number of sites. We also investigated the regulation of beta adrenergic receptors in three age-groups. After 60 min of immobilization stress the number of MNL surface receptors was reduced in young (4-month-old) rats but not in mature (12-month-old) or aged (26-month-old) rats. Using an alternative stress procedure, after single or repeated open-field sessions, we found receptor redistribution and down-regulation, respectively, in young rats. None of these adaptive receptor response was observed in 26-month-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1985

Increased sensitivity to serotonergic agonists after repeated electroconvulsive shock in rats.

The effect of single and repeated electroconvulsive shock (ECS) (once daily for 7 days) on head twitches produced by 5-HT agonists (LiCl, 5-hydroxytryptophan; 5-HTP and 5-methoxytryptamine; 5-MT) was investigated 1 hr, 24 hr, 5 days and 10 days after the last ECS, while locomotor activity induced by serotonergic agonists (fenfluramine, 3-chlorophenylpiperazine; m-CPP) and antagonists (metergoline, cyproheptadine) was only investigated after 24 hr. 5HT and 5-HIAA concentrations were measured 0.5, 1 and 24 hr after a single ECS and up to 10 days after repeated ECS. Head twitches induced by LiCl were significantly depressed 1 hr after both single and repeated ECS. The number of head twitches produced by LiCl, 5-HTP or 5-MT given 24 hr after single or repeated ECS did not change but it rose significantly 5 and 10 days after the last shock. Repeated ECS increased locomotor activity 24 hr after the last shock. This increase was significantly enhanced by serotonergic antagonists. Biochemical assays showed that a single ECS did not significantly change brain 5-HT and 5-HIAA concentrations 0.5, 1 or 24 hr after the ECS. On the other hand, repeated ECS raised brain 5-HIAA 0.5, 1 and 24 hr or 5 and 10 days and 5-HT 0.5 hr after the final ECS. It is concluded that a single or repeated ECS both depress the serotonergic system response to LiCl but repeated ECS facilitates the response to serotoninomimetics.

5-Hydroxytryptophan↗
PubMed1977

Effect of two non tricyclic antidepressant drugs on [14C]5-hydroxytryptamine uptake by rat platelets.

The uptake of 14C-5-HT by rat blood platelets was examined in vitro in experimental conditions which allowed measurement of the initial velocity and excluded other passive processes across the cell membrane. In these conditions, the effect of two non tricyclic antidepressant drugs (Lilly 110140 and trazodone) was investigated. Lilly 110140 was as active as chlorimipramine and several times more active than imipramine as an inhibitor of 14C-5-HT uptake. Like chlorimipramine, Lilly 110140 appeared to be either a non-competitive or an uncompetitive inhibitor, according to the concentration of drug used. Trazodone also inhibited 14C-5-HT uptake by platelets but to a lesser extent than chlorimipramine, imipramine or Lilly 110140. m-Chlorophenylpiperazine, a possible metabolite of trazodone, was about 3 times more potent an inhibitor than the parent molecule. Both compounds acted non-competitively. Compared with published data on the effect of Lilly 110140 and trazodone on brain 5-HT, the present results support the suggestion that rat platelets are a useful pharmacological model of serotoninergic nerve endings.

Animals↗
PubMed1977

Interference by fenfluramine with the storage of 14C-5-hydroxytryptamine in rat platelets.

(+)Fenfluramine decreases the 14C-5HT stored in rat platelets both in in vitro and in in vivo systems, indicating a release of the amine. The effect of (+) fenfluramine in vitro increases by increasing the concentration of the drug, the time of incubation with platelets and the temperature. It is not accompanied by loss of lactate dehydrogenase thus excluding an unspecific damage to the platelet membrane induced by the drug. In addition it is not inhibited either by inhibitors of the uptake of 5HT (chlorimipramine, Lilly 110140) or by inhibitors of the platelet 'release reaction' (acetylsalicylic acid) or by an excess of cold 5HT in the incubation medium. The effect of (+) fenfluramine in vivo is dose-dependent and increases gradually up at least 18 hr after i.p. drug's administration. It is significantly inhibited in rats pretreated by either chlorimipramine or Lilly 110140, but not by acetylsalicyclic acid. In analogy with the effect of (+) fenfluramine on rat brain 5HT, it is suggested that this drug could enter platelets by utilizing the 5HT uptake mechanism, at least in vivo.

Animals↗
PubMed1976

Uptake of 14C-5-hydroxytryptamine by human and rat platelets and its pharmacological inhibition. A comparative kinetic analysis.

In order to approach the uptake of 14C-5HT by platelets as a first-order process, experimental conditions were selected in which accumulation of the amine either by diffusion or by other passive nonsaturable processes could be excluded. These conditions included an incubation period of 14C-5HT with human or rat platelets of 4 min or 30 s, respectively and the use of substrate concentrations around the calculated apparent Km values (0.25 - 2.0 muM). While the apparent Km values were rather similar for human and rat platelets, Vmax was about 5 times higher in rat than in human platelets. The kinetic model adopted in this study was used to evaluate the relative potency and the type of inhibiton of 14C-5HT uptake exhibited by imipramine, chlorimipramine and (+)-fenfluramine. All 3 compounds inhibited 14C-5HT uptake by platelets. Chlorimipramine was about 10 times more effective than imipramine both in rat and in human platelets. Both drugs were more potent inhibitors on human than on rat platelets. (+)-Fenfluramine was almost as active as imipramine on rat but 30 times less potent than imipramine on human platelets. Both imipramine and chlorimipramine inhibited 14C-5HT uptake by an apparent non-competitive mechanism, whereas (+)-fenfluramine appeared to act as a competitive inhibitor. No differences were found in this respect between human and rat platelets. Pharmacological or therapeutic doses of these drugs usually result in plasma concentrations similar to those found in this study to effectively inhibit platelet 14C-5HT uptake.

Adult↗
PubMed1976

The effect of lithium chloride on the activity of some psychotropic drugs.

LiCl administered for 4 days enhances amphetamine-induced locomotor stimulation, increases amphetamine toxicity in aggregated mice but does not affect amphetamine stereotypy. Administered together with nialamide, LiCl increase locomotor activity of mice and rats. The administration of this compound together with reserpine reverses central effects of its action (hypothermia, decreased motility, enhancement of hexobarbital activity).

Amphetamines↗
PubMed1975

Central action of drugs acting on the cholinergic muscarinic receptor I. Influence of cholinomimetic drugs administered into the lateral cerebral ventricle on behavior in rats.

Carbachol (CCh), physostigmine (Pht) and pilocarpine (Pil) injected into the lateral cerebral ventricle (ivtr), diminished spontaneous motility and open-field performance, lowered body temperature, depressed amphetamine-induced hypermotility, and inhibited amphetamine stereotypy. On the other hand, they had no effect on duration of hexobarbital anesthesia, except Pil, which slightly prolonged it, or on the action of threshold dose of pentetrazole and maximal electroshock. The compounds raised levels of "free" and "total" ACh, but not those of "bound" ACh. Level of NA in the brain was decreased, while level of DA was unaltered. These results are further evidence of an inhibitory influence of cholinomimetic drugs on behavior in animals.

Acetylcholine↗
PubMed1975

Central action of drugs acting on the cholinergic muscarinic receptor. II. Influence of ecothiopate administered into the lateral cerebral ventricle on behavior in rats.

Ecothiopate (Etp), 10 mug injected into the lateral cerebral ventricle (ivtr), diminished spontaneous motility and open-field performance, lowered body temperature, inhibited amphetamine-induced hypermotility and stereotypy, prolonged hexobarbital anesthesia and did not induce catalepsy. These behavioral symptoms were accompanied by lowered level of NA and elevated levels of 5-HT and 5-HIAA in the brain. No change in levels of DA were noted. Smaller doses (0-1 and 1 mug) had virtually no influence on behavior of the animals. The dose of 1 mug caused a rise in levels of 5-HIAA in the brain, but had no influence on levels of NA, DA and 5-HT.

Amphetamine↗
PubMed1975

The influence of alkaline elements on the metabolism of 5-hydroxytryptamine in rat's brain.

A single or four time-administration of Li, Na, K, Rb and Cs chlorides at the doses of 2-5 and 5 mEq/kg ip does not significantly affect 5-HT level. The level of 5-hydroxyindoleacetic acid (5-HIAA) increase only after the administration of LiCl. This increase occurs already after 1 hr and persists up to 24 hrs after the last injection. LiCl given together with probenecid induces the increase in 5-HIAA level greater than that after probenecid alone. The decrease in 5-HIAA level after pargyline-induced inhibition in MAO is more rapid in animals submitted to two action of Li. The increase 5-HIAA level in rat's brain results from Li ions-increased 5-HT turnover.

Animals↗