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Biomedical subjects

E Costa

Publications and source records attributed to E Costa.

At least 451 records · Page 25Linked to original sources

Modulation of nicotinic receptors by opiate receptor agonists in cultured adrenal chromaffin cells.

Morphological, physiological and pharmacological evidence indicates that opioid peptides, which in the brain are located intraneurally, may function as neurotransmitters. Similar evidence is not yet available for the opioid peptides that are stored in chromaffin cells of adrenal medulla and in axon terminals located in adrenal medulla and sympathetic ganglia. The present report contributes evidence suggesting that the opioid peptides which are stored in the axon terminals of the splanchnic nerves located in adrenal medulla may function as neuromodulators of the acetylcholine receptors located on chromaffin cells that are involved in catecholamine release. We support this functional role of the opioid peptides by showing that primary cultures of chromaffin cells of bovine medulla contain opiate receptors. When these receptors are occupied by specific agonists, the number of nicotinic receptors and the amount of catecholamine released by maximal doses of nicotine are reduced. Thus, like in other neuronal systems also in adrenal medulla, the action of opioid peptides is inhibitory. The specificity of this action is in part supported by the inability of opiate receptor agonists to reduce the Ca2+-dependent release of catecholamines elicited by K+ ions.

Adrenal Medulla↗

Substance P in the superior cervical ganglion and the submaxillary gland of the rat.

Substance P has been detected in the superior cervical ganglion and submaxillary gland of the rat by radioimmunoassay. Decentralization, section of the carotid sinus nerve, or deefferentation does not affect the level of substance P in the rat superior cervical ganglion. Superior cervical ganglionectomy does not affect the amount of substance P in the submaxillary gland; however, section of the chorda tympani or duct ligation significantly reduces substance P in the submaxillary gland. It is concluded that substance P in the superior cervical ganglion is not located in the preganglionic sympathetic neurons, afferents from the glossopharyngeal nerve or post-ganglionic neurons projecting to the submaxillary gland or carotid body. Substance P does not appear to be associated with sympathetic innervation of the submaxillary gland, but it is anatomically and functionally related to the chorda tympani and possibly involved in the parasympathetic innervation of the gland. Substance P may also be present in gland cells of the submaxillary gland.

Animals↗

Leptospirin - an intradermic test for the diagnosis of leptospirosis.

IN the State of Bahia (Brazil) the leptospirin produced in Germany for experimental use by the Institute for Veterinary Medicine, Federal Health Office, Berlin, was administered to humans and animals in order to diagnose leptospirosis in collaboration with this Institute. The results were compared with the microscopic agglutination reaction. The total number of test persons or animals was 268; this group included 81 human patients. 60 heads of cattle, 50 goats, 40 pigs, 25 horses, and 12 dogs. All were tested serologically and simultaneously the intracutaneous test was carried out. This test was positive when the erythema formed had a diameter of more than 9 mm. The evaluation took place 8 to 10 h and 24 h after the injection of leptospirin. 1. 52 humans reacted serologically; out of this group 44 were positive in the leptospirin test. The allergy test was also negative in the 29 serologically negative patients. 2. Out of the 21 heads of cattle with a positive agglutination test 7 reacted to leptospirin whereas 39 animals which did not react serologically were also negative in the skin test. 3. Although 10 goats out of 50 reacted serologically, all were negative in the intracutaneous test. 4. 9 out of 40 pigs reacted serologically; however, 8 reacted only to apathogenic leptospires (L.patoc, L.rufino, L.andamana). Out of these 9 animals 4 were positive in the intracutaneous test; among them the pig which reacted serologically to L.autumnalis. Out of 31 serologically negative pigs 2 were allergologically positive. 5. Out of 21 serologically positive horses 15 exhibited an erythema which was considered positive in the skin test. 4 serologically negative animals also were negative in the intracutaneous test. 6. Out of 6 serologically positive dogs, 4 reacted to leptospirin. 6 that had reacted serologically were all negative in the intracutaneous test. A comparison of the serological and allergological findings judged by the serological standard showed that out of all cases tested, 0.7% had at the same time a serologically negative and allergologically positive reaction and 16.8% had a serologically positive and allergologically negative reaction. In some cases, the administration of leptospirin caused the formation of antibodies which could only be detected in low dilutions and usually disappeared after 6-8 weeks. In humans, pigs, and horses the leptospirin also showed positive reactions which serologically could be attributed only to biflexa leptospires. Serotypes not contained in the leptospirin were accounted for to a varying degree in the individual animal species. These reactions and the results of other studies carried out in pig stocks have been the basis for studies performed at the Institute for Veterinary Medicine. These studies are expected to contribute to an improvement of the sensitivity of the leptospirin.

Agglutination Tests↗

Benzodiazepines and neurotransmitters.

Benzodiazepines have been shown to change the turnover rate of 5-HT, ACh and catecholamines stored in selected brain areas, but the doses required for these effects are several-fold higher than those which elicit a persistent punished behavior or antagonize isoniazid, bicuculline or picrotoxin convulsion. The selective antagonism against convulsions elicited by drugs that impair GABAergic transmission, the capability of muscimol and other GABA receptors agonists to mimic behavioral and anticonvulsant action of the benzodiazepines have suggested that benzodiazepines facilitate GABA transmission. This facilitation of the GABA tranmission is due to an allosteric facilitation of high-affinity GABA binding to postsynaptic receptors. Also, the high-affinity binding of the benzodiazepines can be facilitated by GABA mimetics. Endogenous inhibitors of the benzodiazepines and GABA binding extracted from synaptic membranes play a role in facilitating these interactions. Using neuroblastoma 2A cells as a model and Cl- influx as an index of GABA receptor activation, it will be shown that the benzodiazepines facilitates not only GABA binding but also its action on Cl- channels. Also, glioma C6 cells have high affinity receptors for GABA and benzodiazepine binding but these binding sites are not linked to a Cl- channel. It is concluded that the benzodiazepines displace a regulatory protein for high-affinity GABA receptors and thereby facilitate GABAergic transmission.

Animals↗

Increase of neurotensin content elicited by neuroleptics in nucleus accumbens.

The content of neurotensin immunoreactive material (neurotensin-IR) of nucleus accumbens increases 16 hr after a single injection of 2 mg/kg i.p. of haloperidol; this increase persists for 8 hr or longer. Repeated injections of 2 mg/kg/day of haloperidol i.p. cause a gradual and progressive increase of neurotensin-IR. From 0.32 pmol/mg of protein, it increases to 0.57 pmol/mg (1 week) to 0.62 pmol/mg (2 weeks) and reaches 0.68 pmol/mg (3 weeks). A significant increase of neurotensin-IR content of nucleus accumbens is obtained with 0.5 mg/kg i.p. daily for 2 weeks. Maximal responses are obtained with 1 mg/kg/day in 3 weeks. The striatal neurotensin-IR content of rats injected for 2 weeks with 1 mg/kg/day of haloperidol is also increased. In these rats, the neurotensin-IR content of preoptic area hypothalamus, septum and amygdala failed to increase. The increase of neurotensin-IR material of nucleus accumbens was elicited also by chloropromazine (6 mg/kg), trifluoroperazine (2 mg/kg) and pimozide (1.5 mg/kg) while promazine (10 mg/kg) and promethazine (25 mg/kg) were ineffective. The increase of neurotensin-IR content caused by haloperidol chloropromazine, trifluoroperazine and pimozide in accumbens and striatum suggests a modulation of neurotensin metabolism, synthesis or utilization directly or indirectly through dopaminergic synapses.

Animals↗

beta Adrenergic receptor-mediated regulation of cyclic nucleotide phosphodiesterase in C6 glioma cells: vinblastine blockade of isoproterenol induction.

Persistent stimulation with isoproterenol of the beta adrenergic receptor located in C6 glioma cell membranes results in a rapid rise in the cyclic AMP content, an activation of soluble cyclic AMP-dependent protein kinase, a translocation of catalytic subunits of the activated protein kinase to the nucleus and a delayed (3--4 hr later) increase of cyclic AMP phosphodiesterase activity and beta-nerve growth factor content. The phosphodiesterase increase requires new RNA and protein synthesis. A pretreatment of the cells with vinblastine in doses that fail to change protein synthesis blocks the increase in phosphodiesterase activity elicited by isoproterenol: the ED50 of vinblastine for this effect is 2.6 x 10(-7) M. In contrast, the simultaneous increase in beta-nerve growth factor content elicited by isoproterenol is not blocked by vinblastine and does not require new RNA and protein synthesis. We conclude that intact microtubules are required to transfer the catalytic subunits of activated protein kinase from cytosol to the nucleus. Hence microtubules may be operative in facilitating communication between the cell membrane and the nucleus.

3',5'-Cyclic-AMP Phosphodiesterases↗