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Biomedical subjects

M Briley

Publications and source records attributed to M Briley.

88 records · Page 5Linked to original sources
PubMed1981

Sodium dependency of [3H]imipramine binding in rat cerebral cortex.

[3H]imipramine binding to membranes prepared from rat brain cortex is sensitive to sodium ions. The dissociation constant, K(D), in the absence of added sodium was four times greater than in the presence of 120 mM sodium chloride. There was no change in the maximal binding, Bmax, of [3H] imipramine binding in the absence of sodium. The addition of Tris chloride in the range of 10-300 mM caused only a small decrease in the binding of [3H] imipramine whereas the addition of similar concentrations of sodium chloride increased linearly the binding of [3H] imipramine at 1 nM by over 100%.

Animals↗
PubMed1981

Regional distribution of [3H]imipramine binding in rat brain.

[3H]imipramine binding was measured in 23 microdissected areas of the rat brain and compared to published values for the endogenous levels of serotonin, noradrenaline and dopamine in the same areas. The density of [3H]imipramine binding sites appears to be highly correlated with the distribution of endogenous serotonin especially where the serotonin is located mainly in nerve terminals. A weak but still significant correlation also exists with the distribution of endogenous noradrenaline whereas no such correlation could be detected for endogenous dopamine.

Animals↗
PubMed1981

Distribution of specific high-affinity binding sites for [3H]imipramine in human brain.

[3H]Imipramine binds with high affinity to membranes from different regions of the human brain. The highest density of binding sites was observed in the hypothalamus and substantia nigra and the lowest density in the white matter and cerebellum. As found in rat brain, tricyclic antidepressant drugs are potent inhibitors of [3H]imipramine binding. Atypical antidepressants are, however, much weaker at inhibiting the specific binding. The [3H]imipramine binding site in human cortex is apparently identical to the site already described in the rat brain and in human platelets.

Aged↗
PubMed1981

Localisation of tricyclic antidepressant binding sites on serotonin nerve terminals.

High-affinity specific [3H]imipramine binding has been demonstrated in the brain and platelets of various species including man. Electrolytic lesions of the rat dorsal raphe, which resulted in a significant decrease in the endogenous levels of serotonin produced a reduction in the density of [3H]imipramine binding sites in the hypothalamus and cortex. The affinity constants were unchanged. These results suggest that [3H]imipramine binding sites are located on serotonin nerve terminals.

Animals↗
PubMed1980

High-affinity [3H]imipramine binding in rat hypothalamus: association with uptake of serotonin but not of norepinephrine.

Inhibition of the binding of [3H]imipramine and inhibition of the uptake of [3H]serotonin and [3H]norepinephrine by a series of antidepressants and other drugs were studied in the rat hypothalamus. No correlation was found between the potencies of these drugs for the inhibition of [3H]imipramine binding and the inhibition of [3H]norepinephrine uptake. There was, however, a highly significant correlation between the potencies of these drugs for the inhibition of [3H]serotonin uptake. These results suggest that high-affinity [3H]imipramine binding might be associated with the mechanism of serotonin uptake in the brain.

Animals↗
PubMed1980

Chronic sympathetic denervation increases muscarinic cholinoceptor binding in the rat submaxillary gland.

Superior cervical ganglionectomy was found to produce a large decrease in the cocaine-sensitive accumulation of 3H-noradrenaline in the rat submaxillary gland, indicating an effective sympathetic denervation. Six weeks after unilateral denervation the muscarinic cholinoceptor binding of 3H-QNB was increased by over 50% compared to the contralateral, innervated gland. There were no differences in the Kd values between the innervated and denervated glands. These results suggest that changes in muscarinic cholinoceptor density might be in part responsible for the postsynaptic supersensitivity to cholinoceptor agonists observed after chronic sympathetic denervation.

Animals↗
PubMed1980

Evidence against beta-adrenoceptor blocking activity of diltiazem, a drug with calcium antagonist properties.

1 The isolated spontaneously beating atria of the rat, diltiazem (0.01 to 0.1 microM) shifted the atrial rate concentration-response curves to isoprenaline to the right in a non-parallel manner and depressed their maxima. Under the same experimental conditions, (+/-)-propranolol (0.03 to 0.1 microM) behaved as a competitive beta-adrenoceptor antagonist. 2 Whereas (+/-)-propranolol (IC50 = 12 nM) and isoprenaline (IC50 = 0.9 microM) inhibited (-)-[3H]-dihydroalprenolol binding to rat brain membrane preparations, diltiazem failed to do so in concentrations up to 10 microM. 3 Diltiazem but not (+/-)-propranolol, antagonized the positive chronotropic responses to calcium in spontaneously beating rat atria. 4 It is proposed that diltiazem inhibited the tachycardia induced by isoprenaline through an effect on calcium which may be an essential modulator of the sequence of events linking the beta-adrenoceptor activation and heart rate response.

Adrenergic beta-Antagonists↗
PubMed1979

Specific tricyclic antidepressant binding sites in rat brain.

The discovery of high-affinity binding sites for psychoactive drugs such as benzodiazepines, opiates and neuroleptics has opened up new approaches to the study of these drugs and their mechanisms of action. Although most tricyclic antidepressants inhibit neuronal uptake of noradrenaline and serotonin, their mechanism of action remains unclear. Changes in the sensitivity of the beta-receptor after chronic tricyclic antidepressant treatment suggest that they modulate noradrenergic neurotransmission. Tricyclic antidepressants also act directly on cholinergic, histaminergic, alpha-adrenergic and serotonergic receptors. It is not clear, however, which, if any, of these effects are related to the primary antidepressant effect or whether they are simply responsible for some of the side effects. We have thus investigated the possibility that specific binding sites for tricyclic antidepressants exist in the central nervous system. So far, binding studies using 3H-labelled tricyclic antidepressant drugs have only detected binding to histaminergic H2 and cholinergic muscarinic receptors and low-affinity binding. We demonstrate here a population of specific high-affinity binding sites for 3H-imipramine on brain membranes which may be responsible for the antidepressant effects of these drugs.

Animals↗
PubMed1979

Specific labelling of postsynaptic alpha 1 adrenoceptors in rat heart ventricle by 3H-WB 4101.

The alpha-adrenoceptor ligand, 3H-WB 4101 binds to a single population of independent sites in the rat heart ventricle. These sites are not affected by chemical sympathectomy with 6-hydroxydopamine and thus appear to be located postsynaptically. The relative order of potencies for displacement of 3H-WB 4101 binding:prazosin greater than phentolamine greater than yohimbine, is characteristic of that of the alpha 1 type of adrenoceptors. In heart ventricle 3H WB-4101 thus seems to label specifically postsynaptically located alpha 1-adrenoceptors. The significance of the specificity of this ligand is discussed with relevance to its use in the central nervous system.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Carnitine acetyltransferase activity is not changed with age in rat brain and human platelets.

Carnitine acetyltransferase activity was studied in different brain regions of the rat and in human platelets. The values of Km for carnitine and for acetyl-CoenzymeA (acetyl-CoA) were similar in cortex, hippocampus and striatum of the rat and in human platelets, suggesting that carnitine acetyltransferase might be a useful peripheral marker of its central activity. The activity of this enzyme was similar in the cortex and hippocampus of young and old rats. Furthermore, the determination of carnitine acetyltransferase activity in platelets from healthy volunteers showed no significant difference with age.

Acetyltransferases↗
PubMedDate not supplied

5-HT autoreceptors in the regulation of 5-HT release from guinea pig raphe nucleus and hypothalamus.

5-HT autoreceptors involved in the regulation of 5-HT release in the guinea pig dorsal raphe nucleus have been studied in comparison with those in the hypothalamus. In vitro release was measured in slices of raphe and hypothalamus prelabelled with [3H]5-HT, superfused with Krebs solution and depolarized electrically. The non-selective 5-HT receptor agonist, 5-carboxamidotryptamine (5-CT) (0.1-10 nM for raphe: 1-100 nM for hypothalamus) and antagonist, methiothepin (10-1000nM), decreased and increased, respectively, the release of [3H]5-HT evoked by electrical stimulation in either of these regions when given alone. The selective 5-HT1B/D receptor antagonist, GR127935 (100-1000 nM), and the 5-HT1D receptor antagonist, ketanserin (300-1000 nM), had no significant effect on this release in either of these regions. Methiothepin and GR127935 (100-1000 nM) shifted to the right the concentration-effect curve of 5-CT in both the raphe and the hypothalamus. At 300 nM, ketanserin shifted to the right the concentration-effect curve of 5-CT in the raphe but did not modify the 5-CT curve in the hypothalamus. In microdialysis experiments ketanserin, applied locally at 10 microM, increased the extracellular levels of 5-HT in the dorsal raphe nucleus of the freely moving guinea pig, whereas 5-HT levels were unchanged in the hypothalamus. Ketanserin at 1 microM did not affect the decrease in 5-HT output induced by the selective 5-HT1B/D receptor agonist, naratriptan (used at 10 microM in raphe and 0.1 microM in hypothalamus), in the raphe or the hypothalamus. In the raphe, WAY100635, a 5-HT1A receptor antagonist, at 1 microM, did not prevent naratriptan (10 microM) from reducing the extracellular levels of 5-HT. These results suggest that, in the conditions used in this study, the release of 5-HT in the dorsal raphe nucleus is possibly modulated in part by 5-HT1B receptors but essentially the control is through 5-HT receptors whose subtype is still to be determined. In the hypothalamus, however, it is clear that only 5-HT1B receptors are involved in the modulation of 5-HT neurotransmission.

Animals↗
PubMedDate not supplied

[Monoaminergic receptors and hypotheses of the mechanisms of action of 2nd generation antidepressive agents].

The inhibition of the serotonin and/or noradrenalin reuptake is often given as the mechanism of action of antidepressants. This may be true but it's certainly wrong! The diversity of chemical structure and pharmacological profiles of second generation antidepressants shows that the biochemical property that is the most often found is the inhibition of the uptake of 5-HT and/or NA. The difference of the kinetics between the inhibition of the monoamine reuptake and the antidepressant effect is only one of the reasons to believe that the real mechanism of their antidepressant action is elsewhere. The different hypotheses that have been proposed will be examined.

Animals↗