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Biomedical subjects

E Costa

Publications and source records attributed to E Costa.

At least 415 records · Page 23Linked to original sources
PubMed1982

Accumulation of hypothalamic endorphins after repeated injections of anorectics which release serotonin.

Two anorectic drugs which stimulate serotonin neuronal activity by releasing serotonin from nerve terminals, d-fenfluramine and CM 57 277 (4-amino-[6-chloro-2-pyridyl]-1-piperidine HCl), were studied in rats. Both drugs, when given for 5 days at doses of 15 mg of d-fenfluramine per kg/day and 20 mg of CM 57 277 per kg/day, decreased body weight gain and increased content of Met5-enkephalin and beta-endorphin in hypothalamus, but not in frontal cortex or pituitary. The increase in the hypothalamic content of the two opioid peptides elicited by d-fenfluramine was reversed by metergoline and p-chlorophenylalanine, suggesting that it is mediated by serotonin. The content of two other hypothalamic neuropeptides, cholecystokinin and substance P, were not affected by d-fenfluramine. Although Met5-enkephalin content in striatum was increased transiently by d-fenfluramine, this was not a serotonin-mediated effect because it was not abolished by metergoline. The decrease in body weight gain was prevented by metergoline, but not by i.p. injection of p-chlorophenylalanine. The effect of p-chlorophenylalanine on intestine may contribute to its failure in reversing the anorectic effect of d-fenfluramine. Naltrexone, an antagonist of opiate receptor, decreased body weight gain but exerted no effect on hypothalamic Met5-enkephalin or beta-endorphin content. Taking into consideration that the increase in Met5-enkephalin and beta-endorphin may have resulted from accumulation due to decreased utilization, the anorectic effects of serotonin releasing drugs may be mediated by a reduction in the functional role of hypothalamic opioid peptides.

Animals↗
PubMed1981

Endogenous inhibitors of Na+-independent [3H]GABA binding to crude synaptic membranes.

The characteristics of the Na+-independent high-affinity binding of [3H]GABA to various types of crude synaptic membranes (CSM) prepared from rat brain cortex were studied. In freshly prepared CSM the content of GABA was so high that the high-affinity [3H]GABA binding could not be determined. In contrast when the frozen-thawed CSM were incubated at 37 degrees for 30 min with or without Triton X-100 or phospholipase C and then washed repeatedly, there was a virtual disappearance of GABA from the supernatant extracts and the binding constants of [3H]GABA to CSM could be determined. Two apparent populations of [3H]GABA binding sites, one with a low- and the other with a high-affinity constant, were detected. The ratio of the number of high- to low-affinity binding sites varies with the method used to prepare the membranes. The lowest value of this ratio was observed with membranes incubated at 37 degrees for 30 min. However, when frozen-thawed CSM were treated with 0.05% Triton X-100 repeatedly, the ratio of the number of high- to low-affinity binding sites increased progressively. This increase in ratio is due to a selective increase in the number of the high-affinity sites without significant changes in the number of the low-affinity sites. The extent of the increase in the number of sites that bind [3H]GABA with high affinity after repeated Triton X-100 treatments was paralleled by a decrease of an endogenous protein which inhibits GABA binding. The reapplication of this endogenous material to membranes repeatedly treated with Triton X-100 reduces the number of high-affinity binding sites for [3H]GABA to values similar to those measured in membranes that were not treated with Triton X-100. The inhibitory preparation extracted from CSM incubated with Triton X-100 was shown to be free of GABA or phospholipids. The gel filtration chromatography reveals the presence of two molecular forms of the inhibitor; of these, the high-molecular-weight material fails to bind GABA, whereas the low-molecular-weight material appears to bind GABA. The high-molecular-weight endogenous inhibitor has been termed GABA modulin.

Amino Acids↗
PubMed1981

Regulation by a beta-adrenergic receptor of a Ca2+-independent adenosine 3',5'-(cyclic)monophosphate phosphodiesterase in C6 glioma cells.

The hormonal control of cyclic nucleotide phosphodiesterase (EC 3.1.4.17) activity has been studied by using as a model the isoproterenol stimulation of cyclic AMP phosphodiesterase activity in C6 glioma cells. A 2-fold increase in cyclic AMP phosphodiesterase specific activity was observed in homogenates of isoproterenol-treated cells relative to control. This increase reached a maximum 3 h after addition of isoproterenol, was selective for cyclic AMP hydrolysis, was reproduced by incubation with 8-Br cycl AMP but not with 8-Br cyclic GMP and was limited to the soluble enzyme activity. The presence of 0.1 mM EGTA did not alter the magnitude of the increase in phosphodiesterase activity. Moreover, the calmodulin content in the cell extracts was not changed after isoproterenol. DEAE-Sephacel chromatography of the 100000 X g supernatant resolved two peaks of phosphodiesterase activity. The first peak hydrolyzed both cyclic nucleotides and was activated by Ca2+ an purified calmodulin. The second peak was specific for cyclic AMP but it was Ca2+- and calmodulin-insensitive. Isoproterenol selectively increased the specific activity of the second peak. Kinetic analysis of the cyclic AMP hydrolysis by the induced enzyme revealed a non-linear Hofstee plot with apparent Km values of 2-5 microM. Cyclic GMP was not hydrolyzed by this enzyme in the absence or presence of calmodulin and failed to affect the kinetics of the hydrolysis of cyclic AMP. Gel filtration chromatography of the induced DEAE-Sephacel peak resolved a single peak of enzyme activity with an apparent molecular weight of 54000.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1981

Dopaminergic modulation of adenylate cyclase stimulation by vasoactive intestinal peptide in anterior pituitary.

The activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by vasoactive intestinal peptide (VIP) was used as a model to investigate the molecular mechanisms triggered by the occupancy of dopamine recognition sites in rat anterior pituitary. Dopamine failed to change the basal enzyme activity, but it inhibited the stimulation of adenylate cyclase elicited by VIP. Apomorphine, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene, and 2-bromo-alpha-ergocryptine mimicked the effect of dopamine, whereas (-)-sulpiride and and classical neuroleptics antagonized it. Dopamine failed to modulate the activation of pituitary adenylate cyclase by prostaglandin E1, which does not increase prolactin secretion. From these results we infer that stimulation of D-2 (dopamine) receptors may affect pituitary secretion by inhibiting the activation of anterior pituitary adenylate cyclase by VIP or other secretagogues.

Adenylyl Cyclases↗