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Biomedical subjects

E Costa

Publications and source records attributed to E Costa.

At least 397 records · Page 22Linked to original sources
PubMed1982

The dimethylheptyl derivative of (-)-delta 8-tetrahydrocannabinol reduces the turnover rate of gamma-aminobutyric acid in the septum and nucleus accumbens.

Accumulating evidence suggests that the cannabinoids exert their action to reduce the turnover rate of acetylcholine in the hippocampus by an action in the septum via inhibitory gamma-butyric acid (GABA) containing interneurons. In the studies presented here administration of the potent dimethylheptyl derivative of (-)-delta-tetrahydrocannabinol, which has previously been shown to reduce the turnover rate of acetylcholine in the hippocampus, reduces the turnover rate of GABA in the septum. A simple model in which cannabinoids transsynaptically activate inhibitory GABAergic septal neurons impinging on cholinergic septal neurons does not explain the data. A more complex model suggesting that inhibitory GABAergic septal interneurons innervate other inhibitory GABAergic septal interneurons has been hypothesized.

Acetylcholine↗
PubMed1982

Different synaptic location of mianserin and imipramine binding sites.

The high-affinity binding sites for mianserin and imipramine appear to be locate in different neurons of rat brain. Studies in which lesions were produced with 5,7-dihydroxytryptamine and other studies in which the 5-hydroxytryptamine content was decreased with p-chlorophenylalanine indicate that some of the imipramine binding sites are on serotonin axon terminals and others are on nonserotonergic synapses. The sites that bind mianserin are on postsynaptic serotonin sites as well as on synapses of other neuronal systems.

5,7-Dihydroxytryptamine↗
PubMed1982

Nociception, enkephalin content and dipeptidyl carboxypeptidase activity in brain of mice treated with exopeptidase inhibitors.

Thiorphan (60 micrograms intracerebrally) increased the met5-enkephalin content of mouse striatum by 30% in 30 min. This increase was no longer evident at 1 hr. If the dipeptidyl carboxypeptidase, inhibited by thiorphan, were located extraneuronally as suggested by De La Baume, Patey and Schwartz (1981), the met5-enkephalin accumulation represents the rate at which the pentapeptide is released extraneuronally. The increase in met5-enkephalin content was accompanied by an inhibition, greater than 80%, of the dipeptidyl carboxypeptidase that degrades striatal met5-enkephalin. Such an inhibition lasted longer then 2 hr. Thiorphan, given to mice intracerebrally, prolonged the latency time to jump off a 54 degree plate. The effects of thiorphan on brain met5-enkephalin content and hot plate latencies were significantly potentiated by bestatin, which inhibits aminopeptidase B and leucine aminopeptidase.

Animals↗
PubMed1982

Distribution of met-enkephalin-Arg6-Phe7 in various tissues of rats and guinea pigs.

A specific and sensitive radioimmunoassay coupled with gel filtration and HPLC was used to demonstrate the presence and to measure MEAP content in stomach, doudenum, ileum, myenteric plexus, colon, heart, lung, pancreas, liver, adrenal and superior cervical sympathetic ganglia of rat and guinea pig. The highest content was found in various parts of intestine, lung and superior cervical sympathetic ganglia, pancreas and liver were practically devoid of immunoreactivity. In these tissues we found that the distribution of MEAP is not parallel to that of metenkephalin (ME). Our assay excludes interferences by high molecular weight MEAP-like peptides, the cardioexcitatory tetrapeptide (Phe-Met-Arg-Phe NH2) and the correspondent acid Phe-Met-Arg-Phe.

Adrenal Glands↗
PubMed1982

Elevation of Met5-enkephalin and beta-endorphin hypothalamic content in rats receiving anorectic drugs: differences between D-fenfluramine and D-amphetamine.

D-Fenfluramine, an anorectic that releases serotonin (5-HT), repeatedly injected in rats (15 mg/kg per day) enhanced the met5-enkephalin and beta-endorphin content of the hyhpothalamus. The onset of this effect was slow, reaching a peak at 5 days; the increase in beta-endorphin gradually declined toward control level while the drug was still being administered although that of met-enkephalin persisted for 15 days. The elevation of the opioid peptide content of the hypothalamus was temporally associated with a slowing in the rate of body weight increase. A transient, small, increase in striatal met-enkephalin content was also induced by repeated D-fenfluramine injections; however the met-enkephalin content of frontal cortex, hippocampus and brainstem was not affected. A modification of the beta-endorphin content of hypothalamus was not seen after acute injection of D-fenfluramine or D-amphetamine but an increase was observed during repeated treatment with D-fenfluramine. Repeated injections of D-amphetamine for 5 days (4.5 mg/kg per day) failed to increase either the met-enkephalin or the beta-endorphin content of the hypothalamus. These data suggest that the anorexia elicited by repeated injections of D-fenfluramine but not that elicited by D-amphetamine, includes a participation by hypothalamic and beta-endorphin stores.

Animals↗
PubMed1982

Down-regulation of beta-adrenergic receptors following repeated injections of desmethylimipramine: permissive role of serotonergic axons.

The injection of desmethylimipramine (DMI) twice daily for 3 weeks reduced the density of beta-adrenergic receptor recognition sites located in crude synaptic membranes prepared from the cortex and hippocampus and attenuated the stimulation of the membrane-bound adenylate cyclase by isoproterenol. Both actions were abolished if prior to treatment with desmethylimipramine the serotonergic axons were destroyed by an intraventricular injection of 5,7-dihydroxytryptamine. These results show that the down-regulation of beta-adrenergic receptors elicited by repeated injections of desmethylimipramine occurs only if the serotonergic axons are intact.

5,7-Dihydroxytryptamine↗
PubMed1982

Neuronal location of the bombesin-like immunoreactivity in the central nervous system of the rat.

The immunohistochemical distribution of bombesin-like immunoreactivity in the central nervous system of the rat was revealed using a rabbit antibody against [Glu7]bombesin(6-14). In radioimmunoassay, the antibody had minimal cross reactivity with substance P thereby enhancing the significance of histochemical controls proving that the immunoreactivity detected was related to bombesin but not to substance P. Bombesin-immunoreactive neurons were detected in several brain structures including the hypothalamus, interpeduncular nucleus, central grey, dorsolateral tegmental nucleus, dorsal parabrachial nucleus, nucleus of the solitary tract and trigeminal complex. In the spinal cord, intense immunoreactivity was found in the superficial layers of the posterior horn. Since in this area the reaction diminished after rhizotomy the location of the peptide in afferent neurons was considered. In the anterior horn the bombesin-like immunoreactivity located in nerve terminal-like structures was unchanged after rhizotomy suggesting that the cell bodies were located in CNS.

Animals↗
PubMed1982

Isolation, characterization, and purification to homogeneity of a rat brain protein (GABA-modulin).

gamma-Aminobutyric acid (GABA)-modulin is a brain neuropeptide that appears to modulate specific high-affinity (20 nM) GABA recognition sites in brain. When added to crude synaptic membranes this peptide inhibits binding of [3H]GABA to the high-affinity site and prevents facilitation of [3H]diazepam binding elicited by GABA. GABA-modulin has been purified to homogeneity by ammonium sulfate precipitation, gel chromatography, and reverse-phase HPLC. Homogeneity was confirmed by a variety of means, including chromatography under four different HPLC conditions, two different polyacrylamide gel electrophoreses, and end group analysis. Purified GABA-modulin contains approximately 126 amino acids and has a molecular weight of 16,500. The GABA-modulin molecule contains an abundance of hydrophilic basic residues, and neither cysteine nor GABA is present. End group analyses of GABA-modulin showed that histidine is the free COOH terminus and the NH2 terminus is blocked. GABA-modulin specifically blocked both [3H]GABA binding to synaptic membranes (IC50, 0.5 microM) and GABA-stimulated [3H]diazepam binding; the binding of [3H]GABA to low-affinity sites was not affected.

Amino Acids↗
PubMed1982

Opioids regulate cGMP formation in cloned neuroblastoma cells.

Opioid agonists caused a rapid dose-related elevation of the cGMP content of N4TG1 murine neuroblastoma cells. An excellent correlation was found between the rank order of potency of agonists in stimulating cGMP accumulation and in displacing [(3)H]etorphine ([(3)H]ETP) bound to intact cells. The narcotic antagonists naloxone and diprenorphine failed to increase cGMP content; moreover, in the presence of 5 muM naloxone, the EC(50) of ETP increased from approximately 9 nM to > 1 muM. N4TG1 cells that had been incubated for 20 min with 0.32 muM ETP and thoroughly washed displayed a marked loss in sensitivity to subsequent ETP challenge. This desensitization was characterized by a 40-50% decrease in maximal response and an increase in the apparent K(a) of ETP from 4 to 50 nM. Desensitization was complete after a 7-min incubation with 0.32 muM ETP (t((1/2)) approximately 1 min) and was only slowly reversible (t((1/2)) > 60 min). Naloxone (5 muM) and diprenorphine (0.1 muM) failed to elicit desensitization, but they blocked ETP-induced desensitization. Dextrophan and (+)-ethylketazocine were <1% as effective as levorphanol and (-)-ethylketazocine, respectively, in both stimulating cGMP accumulation and inducing desensitization. When the binding of [(3)H]ETP (0.2-20 nM) was examined under identical experimental conditions, cells that were completely desensitized by incubation with ETP (7 min with 0.32 muM or 20 min with 15 nM) showed no loss of high-affinity recognition sites. After longer incubation with ETP (0.32 muM for 20-60 min), the maximal binding of [(3)H]ETP was reduced 17-41%. The specific short-term desensitization of cGMP accumulation is not mediated or accompanied by a decrement in the number of agonist binding sites.

Journal Article↗
PubMed1982

Evidence for ascending and descending intraspinal as well as primary sensory somatostatin projections in the rat spinal cord.

Somatostatin distribution was measured quantitatively in the rat spinal cord by radioimmunoassay. Rostro-caudally, somatostatin content was about 50% higher in lumbar-sacral cord than in cervical or thoracic levels. The dorso-ventral distribution is more uneven: somatostatin is highest in the dorsal horn, where the peptide is 15 times as concentrated as it is in the ventral white matter, the region of lowest concentration. However, measurable amounts of the peptide were found in all regions studied. Dorsal root ganglionectomy decreased somatostatin levels in the dorsal cord, supporting the previously proposed role for this peptide as a primary sensory neurotransmitter or modulator; but somatostatin content also was decreased both rostral and caudal to spinal transection, indicating the presence of ascending and descending somatostatin pathways within the spinal cord. Brain levels did not change. Met-enkephalin and substance P were also measured after the above surgical manipulations. Met-enkephalin content was not altered and substance P content was lowered significantly only after ganglionectomy. Although this study confirms the primary sensory neuron as the origin of a part of spinal cord somatostatin, it further indicates the presence of ascending and descending somatostatin pathways within the rat spinal cord.

Animals↗
PubMed1982

Increase in exogenous choline fails to elevate the content or turnover rate of cortical, striatal, or hippocampal acetylcholine.

The present experiments were designed to test whether increasing the availability of choline to rat brain increases the rate of acetylcholine synthesis in that organ. The content of choline and acetylcholine and the turnover rate of acetylcholine in striatum, hippocampus, and cerebral cortex were measured following changes in dietary choline, intraperitoneal choline, or intravenous infusion of choline. Increasing plasma choline caused some increase in tissue choline but did not increase acetylcholine levels nor acetylcholine turnover rate in any of the areas of brain studied. Indeed, in hippocampus, choline decreased the turnover rate of acetylcholine.

Acetylcholine↗
PubMed1982

Specific high-affinity binding of L-[3H]aspartate to rat brain membranes.

The binding of L-[3H]aspartate was investigated in washed membranes prepared from whole rat brain. We were able to differentiate two separate binding sites differing in their Na dependence. The Na-independent binding was saturable, reversible, and optimal at 20 degrees C and at pHs in the neutral range. The dissociation constant (Kd) at 20 degrees C was about 200 nM. This binding site seemed to be modulated by magnesium and calcium at physiological concentrations. None of the amino acids tested was a potent competitor for Na-independent L-[3H]aspartate binding. This binding site was unevenly distributed in the rat central nervous system: cerebellum = cerebral cortex greater than pons-medulla greater than spinal cord. Destruction of the intrinsic neurons of the cerebellum by injecting kainic acid 30 days before sacrifice resulted in a 53% reduction in Na-independent binding in this region. The Na-dependent binding of L-[3H]-aspartate (Kd = 4894 nM) was strongly inhibited by D-aspartate, L-glutamate, D,L-aspartate beta-hydroxamate; was unaffected by calcium and magnesium; and showed a different pattern of distribution: cerebral cortex greater than cerebellum = pons-medulla = spinal cord. This binding in cerebellum was unaffected by injections of kainic acid.

Animals↗
PubMed1982

Inhibition of acetylcholine turnover rate in rat hippocampus and cortex by intraventricular injection of adenosine analogs.

The effects of i.c.v. administration of adenosine receptor agonists and antagonists on the turnover rate of acetylcholine (TRACh) in various areas of the rat brain were examined in an effort to better understand the role of adenosine as a neuromodulator or cotransmittr. TRACh was determined by gas chromatographic-mass fragmentographic analysis of the rate of deuterium incorporation into ACh and choline during a constant rate infusion of deuterated phosphorylcholine. The i.c.v. administration of the adenosine receptor agonist, 2-chloroadenosine (2-CIAdo), in a dose of 82 nmol failed to change the ACh or choline content of any of the brain areas examined. This dose of 2-CIAdo elicited significant reductions in the TRACh in both the hippocampus and frontal cortex, but not in the striatum. The extent of the TRACh reduction was 67 and 36% in hippocampus and cortex, respectively. This inhibition of TRACh elicited by 2-CIAdo was antagonized by pretreatment (i.c.v.) with theophylline (278 nmol), suggesting that an activation of adenosine receptors is operative in the action of 2-CIAdo. Further support for a participation of adenosine receptors in the action of 2-CIAdo was obtained by comparing the effects of the L- and D-isomers of phenylisopropyladenosine (PIA) on TRACh. The i.c.v. administration of L-PIA (65 nmol) elicited a 79% reduction in the TRACh in the hippocampus, whereas D-PIA (65 nmol i.c.v.) had no significant effect on hippocampal TRACh. This finding supports the view that these effects on TRACh may be mediated by adenosine A1 receptors, but not by A2 receptors, because the former, but not the latter, display marked stereoselectivity toward PIA. It also was demonstrated that intraseptal injections of L-PIA or theophylline failed to reduce the TRACh in the hippocampus, suggesting that adenosine receptors located in the septum are not operative in mediating the i.c.v. action of PIA.

2-Chloroadenosine↗