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Biomedical subjects

E Costa

Publications and source records attributed to E Costa.

At least 433 records · Page 24Linked to original sources
PubMed1981

Regulation of acetylcholine receptors by endogenous cotransmitters: studies of adrenal medulla.

The coexistence of neuropeptides and amine transmitters in the same neuron and the presence of postsynaptic receptors for these compounds invite speculation that the compounds may interact postsynaptically. To study this interaction, we selected the synapse between the splanchnic nerve and the chromaffin cells of adrenal medulla because the splanchnic nerve contains acetylcholine and neuropeptides (multiple molecular forms of enkephalin-like peptides), while the membranes of chromaffin cells contain receptors for acetylcholine and opiate peptides. When the opiate receptors are occupied by specific agonists, these agonists inhibit the expression of acetylcholine receptors. Both the acetylcholine binding and catecholamine release by acetylcholine were inhibited. It is suggested that peptides and acetylcholine coexisting in the splanchnic nerve might act as cotransmitters, there by modulating the sensitivity of acetylcholine receptors. Multiple molecular forms of enkephalin-like peptides are stored in chromaffin cells and are released by acetylcholine. A role for the opiate receptors in the modulation of the secretion of opiate peptides stored in chromaffin cells is not evident.

Adrenal Medulla↗
PubMed1981

A comparative study on the effects of morphine on central, peripheral and ganglionic stores of catecholamines.

The turnover and metabolism of catecholamines after i.p. administration of 10 (low dose) or 40 (high dose) mg/kg of morphine sulfate were measured in the brain, lumbar spinal cord, heart, celiac and superior cervical ganglia (SCG) of demedullated rats with unilaterally decentralized SCG. Demedullation significantly increased norepinephrine concentration and turnover in both sham operated and decentralized SCG, but demedullation failed to change the turnover of dopamine (DA) in both ganglia. Low doses of morphine only increased DA metabolism in the caudate nucleus. High doses of morphine failed to change the turnover of norepinephrine stored in heart and sympathetic ganglia but produced variable changes in norepinephrine turnover in the spinal cord and brain. High doses of morphine significantly increased DA turnover and metabolism in the celiac ganglion, SCG, caudate nucleus and the spinal cord of demedullated rats. These effects of morphine were antagonized by naloxone. DA metabolism in decentralized SCG of demedullated and SCG of intact rats remained unchanged after high doses of morphine. The action of morphine on DA metabolism was facilitated by demedullation, suggesting that the adrenal medulla secretes a modulator that can counteract the effects of opiate ligands on ganglionic small intensely fluorescent cells. Atropine and hexamethonium failed to antagonize the increase in the metabolism of ganglionic DA produced by morphine; and the increase in ganglionic DA metabolism caused by oxotremorine was not antagonized by naloxone, thus confirming a disassociation between the action on ganglionic DA mediated by cholinergic and opiate receptors. Since decentralization of the SCG abolishes the increase in DA metabolism induced by morphine, stimulation of extraganglionic opiate receptors reflects the metabolism of DA located in small intensely fluorescent cells.

Adrenal Medulla↗
PubMed1981

Characterization of benzodiazepine and gamma-aminobutyric recognition sites and their endogenous modulators.

The solubilization and partial purification from rat brain cortex homogenates of [3H]gamma-aminobutyric acid (GABA) and [3H]diazepam recognition sites and of their endogenous modulators (GABA-modulin and an endogenous compound which specifically bound [3H]diazepam) are reported. A high percentage of GABA binding sites (virtually free of benzodiazepine binding sites) was solubilized from homogenates of rat brain cortex incubated at 0 degree C with 1% Triton X-100 and a mixture of protease inhibitors. A large proportion of benzodiazepine binding sites was solubilized in the absence of apparent GABA binding capacity by incubating crude synaptic membrane preparations at 37 degree C with 0.05% Triton X-100. The characteristics of these two solubilized binding sites resemble those of the membrane-bound binding sites. However, unlike the membrane-bound sites, solubilized GABA and benzodiazepine binding sites are insensitive to GABA stimulation, while solubilized GABA binding sites are no longer protected by the benzodiazepines against heat inactivation. These results indicate that GABA and benzodiazepine recognition sites reside in two different molecules which, when bound to membranes, can interact reciprocally and modulate their binding affinity for specific ligands.

Animals↗
PubMed1980

The effect of kainic acid on the hippocampal content of putative transmitter amino acids.

The time courses of the changes in the contents of GABA (gamma-aminobutyric acid), glutamate, aspartate, taurine, glycine and alanine were measured in both hippocampi of rats which were rejected in one hippocampus with kainic acid (KA). The contents of these amino acids were measured with high performance liquid chromatography. The hippocampal contents of GABA, glutamate, aspartate and taurine were reduced homolaterally to the KA injection; in contrast, the contents of glycine and alanine failed to change. The extent of the reductions of GABA, glutamate, aspartate and taurine was dependent on the size of the lesion caused by KA. The greatest decrease occurred after two simultaneous injections of KA, in dorsal and ventral hippocampus. An analysis of the amino acids at different levels of the hippocampus after dorsal injections of KA showed that in the hippocampus the amino acidergic axons do not travel longitudinally. This study suggests that GABA, glutamate, aspartate and taurine are preferentially located in intrinsic hippocampal neurons with short axons.

Amino Acids↗
PubMed1980

Down regulation of dihydroalprenolol and imipramine binding sites in brain of rats repeatedly treated with imipramine.

In rats receiving repeated injections of imipramine, there is a reduction in the number of high affinity binding sites for [3H]imipramine and [3H]dihydroalprenolol present in crude synaptic membrane preparations from various brain structures. The location of the sites that become subsensitive to the two ligands did not coincide; the binding sites to [3H]imipramine became subsensitive in the hippocampus but not in cortex or cerebellum. In contrast the binding sites to [3H]dihydroalprenolol became subsensitive in cortex and cerebellum but not in hippocampus. It can be suggested that in rats repeatedly treated with imipramine the down regulation of beta-adrenergic receptors may not coincide with the down regulation of the high affinity binding sites for imipramine. Such a dissociation is supported further by experiments with rats treated with iprinidol.

Alprenolol↗
PubMed1980

Potentiation by intraventricular muscimol of the anticonflict effect of benzodiazepines.

The anticonflict action of muscimol (a potent GABA receptor agonist) and its ability to potentiate the anticonflict action of the benzodiazepines was studied in rats using VOgel's procedure. Rats were injected intraventricularly with a dose of muscimol from 50 to 200 ng to study whether the anticonflict action was dose-related. The potency of a 200 ng dose of muscimol is comparable to the potency of an anticonflict dose of 0.5 mg i.v. of diazepam. THIP (a muscimol analogue with weaker intrinsic GABA-mimetic activity) is active in doses 10 times higher than muscimol. The threshold dose of diazepam (0.2 mg/kg i.v.) to elicit anticonflict action was markedly potentiated when it was injected 5 min after intraventricular muscimol (150 ng). These data support the concept that GABA receptors may be involved in the anticonflict effects of the benzodiazepines.

Animals↗
PubMed1980

Reduction of hippocampal acetylcholine turnover in rats treated with (-)-delta 8-tetrahydrocannabinol and its 1',2'-dimethyl-heptyl homolog.

The effects of (-)-delta 8-tetrahydrocannabinol (THC), (+)-delta 8-THC, and the dimethyl-heptyl (DMH) homolog of (-)-delta 8-THC (delta 8-THC-DMH) have been compared with the action of (-)-delta 9-THC on the turnover rate of acetylcholine in various brain areas. The data demonstrate that (-)-delta 8-THC-DMH, (-)-delta 9-THC and (-)- delta 8-THC all specifically reduce ther turnover rate of acetylcholine in the hippocampus in a dose-dependent manner ((-)-delta 8-THC-DMH > (-)-delta 9-THC > (-)-delta 8-THC) without altering the acetylcholine or choline content (except for high doses of (-)-delta 8-THC-DMH). The (+)-isomer of delta 8-THC fails to change any cholinergic parameter. The selectivity of action suggests that the tetrahydrocannabinoids may activate specific transmitter receptors which indirectly modulate the activity of the cholinergic neurons in the septal-hippocampal pathway.

Acetylcholine↗
PubMed1980

Changes of hippocampal Met-enkephalin content after recurrent motor seizures.

Kainic acid (KA), a powerful neurotoxic analogue of glutamate, has been extensively used as a tool for selectively lesioning neuronal cell bodies; however, axons or nerve terminals are spared from damage in the area injected with kainic acid. Injections of this neurotoxin in various brain regions were successfully used to locate cell bodies of neurones containing substance P, enkephalin and other putative neurotransmitters. While attempting to locate the cell bodies of the enkephalin containing neurones present in hippocampus using KA injections, we found that a few days after intracerebral injections of KA a drastic increase in the Met-enkephalin (ME) content of hippocampus occurs. We now describe the delayed increase in hippocampal ME content elicited by intracerebral KA injections and examine the possible mechanism that is operative in causing this increase. Moreover, we provide some evidence suggesting that the increase in ME content elicited by intracerebral injections of KA may be related to the recurrent motor seizures elicited by intracerebral injections of KA.

Animals↗
PubMed1980

Protein kinase translocation following beta-adrenergic receptor activation in C6 glioma cells.

Incubation of C6 glioma cells with isoproterenol elicits an increase in cyclic AMP content, followed by an activation of cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). The cytoplasm of these glioma cells contains type II protein kinase and a small amount of cyclic AMP-independent protein kinase. Following the persistent activation of cyclic AMP-dependent protein kinase, catalytic subunits of this enzyme redistribute into particulate fractions. A maximal increase in nuclear protein kinase activity occurrs 45 to 60 min following isoproterenol. The addition of cyclic AMP or of Ca2+ with or without the specific ionophore A-23187 fails to increase the protein kinase activity of nuclei from control or isoproterenol-treated cells. Preincubation of the cells with vinblastine blocks the increase of nuclear protein kinase activity due to isoproterenol. If the incubation with vinblastine occurs simultaneously with isoproterenol, vinblastine fails to reduce the increase in nuclear protein kinase activity elicited by isoproterenol.

Animals↗
PubMed1980

Combination of enzymatic and mass fragmentographic assays for the identification and measurement of [met5]-enkephalin.

Dipeptidyl-aminopeptidase I (DAP I) was used to hydrolyze the pentapeptide-[met5]-enkephalin into the dipeptides Tyr-Gly and Gly-Phe and methionine. The dipeptides could be derivatized and resolved by gas chromagraphy (GC); quantification of these dipeptides was obtained by single ion monitoring. Tissue samples were prepurified with Bio-Beads SM-2 and used as substrate for DAP I. The yield of methionine and of the two dipeptides increases with time. Since the same dipeptides are produced by [met5]-enkephalin (ME) and [leu5]-enkephalin, the use of the ratios of the quantities of the two dipeptides with methionine could be used for recognition. Since the only internal standard available was one with deuterated methionine, the measurement of methionine released by DAP I from the prepurified tissue could be used to measure ME content in tissues that contain a small amount of heterogeneity in the molecular forms of ME. The present GC-mass spectrometric method can be used to quantify ME in brain but not in adrenal medulla because this tissue contains a high degree of molecular heterogeneity.

Animals↗