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M J Gilbert

Publications and source records attributed to M J Gilbert.

28 records · Page 2Linked to original sources
PubMed1991

Evidence that the 5-HT3 receptors of the rat, mouse and guinea-pig superior cervical ganglion may be different.

1. Using grease-gap recordings from the isolated superior cervical ganglion of mouse, rat and guinea-pig, we have compared the depolarization evoked by 5-hydroxytryptamine (5-HT) with that evoked by the selective 5-HT3 receptor agonist 2-methyl-5-HT (2-Me-5-HT). 2. The maximum depolarization induced by 2-Me-5-HT was smaller than that induced by 5-HT in all three species, and particularly in the guinea-pig. 3. The 5-HT2 receptor antagonist ketanserin (1 microM) caused a clear rightward shift of the dose-response curve to 5-HT on the guinea-pig ganglion, but not on the mouse or rat ganglion. Spiperone (0.03 microM) had a quantitatively similar action to ketanserin (0.1 microM) on the 5-HT dose-response curve of the guinea-pig ganglion. Ketanserin had no significant effect on the dose-response curve to 2-Me-5-HT on any of these ganglia. 4. Using 2-Me-5-HT as the agonist, we determined the pA2 values for two 5-HT3 receptor antagonists. The potency of ICS 205-930 varied by approximately 100 fold between the species and that of (+)-tubocurarine varied by over 1000 fold. The differences in the pA2 values of these compounds varied independently among the species. 5. We conclude that 5-HT3 receptors are present on the superior cervical ganglion from the rat, mouse and guinea-pig, but these receptors may be pharmacologically distinct from each other. In addition, the depolarization of the guinea-pig superior cervical ganglion by low concentrations of 5-HT is largely mediated by ketanserin-sensitive receptors.

Animals↗
PubMed1990

A novel series of non-quaternary oxadiazoles acting as full agonists at muscarinic receptors.

1 A novel series of non-quaternary oxadiazole-based muscarinic agonists demonstrated high affinity for muscarinic receptors. 2. These agonists possessed high efficacy in the nanomolar range at muscarinic receptors in the superior cervical ganglion, atrium and ileum but did not show selectivity across the tissue preparations. 3. Two amino oxadiazoles, one from a quinuclidine series (L-660,863) and one from a 1-azanorbornane series (L-670,207) possessed a high ratio of potency for displacing the binding of [3H]-N-methyl-scopolamine ([3H]-NMS) to potency for displacing the agonist [3H]-oxotremorine-M cortex. 4. The two azanorbornane derivatives L-670,548 and L-670,207 stimulated the turnover of phosphatidylinositol in the cortex with a potency higher than that obtained with any other known muscarinic agonist (ED50 0.26 and 0.18 microM respectively). 5. The maximum response obtained with L-670,207 was greater than that observed for carbachol but was comparable to that of the natural ligand acetylcholine. 6. These oxadiazole muscarinic agonists are among the most potent and efficacious non-quaternary muscarinic agonists ever described.

Animals↗
PubMed1989

Hexahydrodifenidol does not distinguish among M1 receptors in rat cerebral cortex, hippocampus and superior cervical ganglion.

We have determined the antagonist affinity of hexahydrodifenidol in a range of receptor assays in the rat:-radioreceptor binding and phosphatidyl-inositol turnover assays in cerebral cortex and hippocampus, and electrophysiological experiments on the superior cervical ganglion and hippocampus. We failed to detect any appreciable differences in the affinity of hexahydrodifenidol among any of these assays.

Animals↗
PubMed1989

Biphasic dose-response curve to muscarine on the rat superior cervical ganglion.

The dose-response curve for the muscarine-induced depolarisation of the rat isolated superior cervical ganglion, studied over the concentration range of 3 nM-1 mM, was biphasic. An apparent maximum was obtained at around 1-3 microM muscarine, but this was only a plateau between the two parts of the curve. Two cardioselective antagonists, gallamine (10 microM) and AF-DX 116 (1 microM) had a complex action on this dose-response curve. The dose-response curve between 0.01 and 0.3 microM was shifted to the right, the responses around 3 microM muscarine were enhanced, but the dose-response curve over 30 microM muscarine was unaffected. The M1-selective antagonist pirenzepine (0.05 microM) depressed all parts of the dose-response curve, but it still appeared biphasic. Pretreatment of the ganglion with pertussis toxin (1 microgram/ml) enhanced the depolarisation to muscarine 0.01-1000 microM and the dose-response curve became less biphasic. Like gallamine and AF-DX 116, pertussis toxin abolished the muscarinic M2-mediated hyperpolarisation of the ganglion recorded in 0.3 microM pirenzepine. It is concluded that the presence of an underlying M2-mediated hyperpolarisation contributes to the biphasic nature of the dose-response curve to muscarine.

Animals↗
PubMed1989

Pertussis toxin sensitivity of drug-induced potentials on the rat superior cervical ganglion.

We have investigated the action of pertussis toxin on a range of receptor-mediated responses of the rat superior cervical ganglion in vitro. The ganglia were treated with pertussis toxin for 24 h at 37 degrees C using an in vitro method. Appropriate controls were also carried out. Pertussis toxin (1 microgram/ml) reduced ganglionic hyperpolarisations mediated by adenosine, alpha 2, 5-HT1A, M2 and GABAB receptors. The GABAB-mediated hyperpolarisation of this preparation, evoked by baclofen and GABA in a bicuculline-resistant manner, has not previously been reported. Pertussis toxin did not reduce ganglionic depolarisations evoked by potassium chloride and 5-HT3, GABAA and nicotinic receptors. Depolarisations to muscarine and noradrenaline, probably mediated by M1 and beta-receptors, also appeared to be resistant to pertussis toxin. The similar sensitivity of the various ganglionic hyperpolarisations to pertussis toxin indicates that they may all be mediated by similar G-proteins.

Animals↗
PubMed1989

5-Hydroxytryptamine evokes three distinct responses on the rat superior cervical ganglion in vitro.

In addition to the 5-HT3-mediated fast depolarisation, 5-hydroxytryptamine (5-HT) evoked two additional responses on the rat superior cervical ganglion: a hyperpolarisation and a slow depolarisation. These responses appeared to be direct actions on 5-HT receptors since they were present in a low calcium medium containing tetrodotoxin and were not abolished by a variety of non-serotonin antagonists. The hyperpolarisation was not antagonised by 5-HT3 or 5-HT2 antagonists. The 5-HT1 ligands 5-carboxamidotryptamine (5-CT) and 8-OH-DPAT also evoked a hyperpolarisation. The hyperpolarisation was antagonised by six 5-HT1A antagonists including WB-4101 and spiroxatrine. It was therefore concluded to be mediated by a 5-HT1A receptor. The slow depolarisation was only evoked by 5-HT. The receptor involved in this response, however, could not be determined. We conclude that in addition to 5-HT3 receptors the rat superior cervical ganglion possesses 5-HT1A receptors and another uncharacterised 5-HT receptor.

Animals↗
PubMed1987

A 5-HT1-like receptor mediates a sympathetic ganglionic hyperpolarization.

5-HT induced a hyperpolarization of the rat superior cervical ganglion in vitro which was resistant to both MDL 72222 (10 microM), a 5-HT3 antagonist, and ketanserin (1 microM), a 5-HT2 antagonist. The 5-HT1-selective ligands 5-carboxamidotryptamine and 8-OH-DPAT also hyperpolarized the ganglion. The 5-HT-induced hyperpolarization was potently antagonised by spiperone. These results suggest that 5-HT hyperpolarizes the rat superior cervical ganglion via a 5-HT1-like receptor which resembles the central 5-HT1A binding site.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMedDate not supplied

The anthropologist as alcohologist: qualitative perspectives and methods in alcohol research.

As research disciplines differ from each other in terms of their epistemological and theoretical assumptions, they differ in the kinds of data they produce. This paper discusses the particular perspectives and methods that anthropologically produced data contribute to a biopsychosocial paradigm of alcohol use/pathology. Strategic uses of qualitative research approaches are suggested, and situations in which qualitatively produced data would be especially useful in the design and delivery of alcohol-related services are identified.

Alcohol Drinking↗
PubMedDate not supplied

Psychosocial and cognitive correlates of alcohol use in younger adult immigrant and U.S.-born Hispanics.

Hispanic groups, taken together, constitute nearly 9% of the U.S. population. Research undertaken in the last decade has demonstrated that segments of the Hispanic male population are particularly heavy drinkers and are at high risk for alcohol-related problems. This article reviews several of the most important studies of alcohol use and its consequences among Hispanics, and reports new data from a study of alcohol use and its correlates among 452 young adult men and women in Los Angeles. The findings show important differences between immigrants and U.S.-born Hispanics as well as clear gender differences in terms of alcohol use patterns, expectations about the benefits of alcohol consumption, and depressive symptomatology associated with the use of alcohol. These differences have implications for the design of prevention and treatment services for Hispanics and these are discussed.

Acculturation↗