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Biomedical subjects

M Schächter

Publications and source records attributed to M Schächter.

7 recordsLinked to original sources
PubMed1986

Desipramine treatment in normal subjects. Effects on neuroendocrine responses to tryptophan and on platelet serotonin (5-HT)-related receptors.

Normal subjects took the tricyclic antidepressant, desipramine hydrochloride, for 16 days. Following treatment there was an increase in the number of specific binding sites on the platelet for both tritiated imipramine and tritiated LSD, the latter site probably representing a platelet serotonin (5-HT) receptor. During desipramine treatment the prolactin response to tryptophan (L-tryptophan) was enhanced, and this enhancement correlated with the increase in platelet LSD binding. The results confirm previous observations that desipramine administration increases certain 5-HT-mediated neuroendocrine responses. Our findings further indicate that desipramine may alter both 5-HT uptake and 5-HT receptor sensitivity, and suggest that the platelet LSD receptor may in certain conditions provide a useful model of 5-HT receptors in the brain.

Adult↗
PubMed1985

Serotonergic agonists stimulate inositol lipid metabolism in rabbit platelets.

The metabolism of inositol phospholipids in response to serotonergic agonists was investigated in rabbit platelets. In platelets prelabelled with [3H]-inositol, in a medium containing 10 mM LiCl which blocks the enzyme inositol-1-phosphatase, 5-hydroxytryptamine (5-HT) caused a dose-dependent accumulation of inositol phosphates (IP). This suggests a phospholipase-C-mediated breakdown of phosphoinositides. Ketanserin, a selective 5-HT2 antagonist, was a potent inhibitor of the 5-HT response, with a Ki of 28 nM, indicating that 5-HT is activating receptors of the 5-HT2 type in the platelet. Lysergic acid diethylamide (LSD) and quipazine also caused dose-related increases in inositol phosphate levels, though these were considerably less than those produced by 5-HT. These results show that relatively small changes in phosphoinositide metabolism induced by serotonergic agonists can be investigated in the rabbit platelet, and this cell may therefore be a useful model for the study of some 5-HT receptors.

Animals↗
PubMed1985

Increased platelet membrane [3H]-LSD binding in patients on chronic neuroleptic treatment.

Using a [3H]-lysergic acid diethylamide [( 3H]-LSD) binding technique, platelet 5-hydroxytryptamine (5-HT) receptor number and affinity were compared in schizophrenics treated with depot thioxanthenes and phenothiazines and controls. There was an approximately 30% increase in platelet receptor number (Bmax) in the patient group. There was a decrease in affinity (increase in Kd) of about 30% in the patient group. This was probably due to the persistence of the neuroleptic in the platelet membrane preparation. There was a weak positive correlation between receptor number and total neuroleptic dosage. The increased number of 5-HT receptors is consistent with the previously reported enhancement of 5-HT-induced platelet aggregation in patients treated with long-term phenothiazines and thioxanthenes. Our findings are compatible with 5-HT up-regulation in human platelets produced by depot neuroleptic therapy. It is not known whether parallel changes may be occurring in brain 5-HT receptors.

Adult↗
PubMed1984

Characterisation of [3H]lysergic acid diethylamide binding to a 5-hydroxytryptamine receptor on human platelet membranes.

Specific binding of [3H]lysergic acid diethylamide (LSD) to human platelet membranes, as defined by 300 nM spiperone, was saturable over the concentration range of 0.25-2.5 nM [3H]LSD. At 0.5 nM [3H]LSD the half-time for association at 37 degrees C was 56 min, half-time for dissociation was 173 min, and the kinetically derived affinity was 0.24 nM. In 19 control subjects equilibrium binding studies gave an affinity of 0.53 +/- 0.02 nM (mean +/- S.E.M.) and capacity of 57.1 +/- 5.6 fmol/mg protein (mean +/- S.E.M.). The inhibition profile was consistent with that of a 5-hydroxytryptamine (5-HT) receptor. There was a significant correlation between the inhibition of [3H]LSD binding and the inhibition of 5-HT-induced shape change, but not inhibition of active platelet uptake of 5-HT. There was also a significant correlation between the inhibition of [3H]LSD binding to human platelet membranes and human frontal cortex. Platelet [3H]LSD binding may therefore be a useful model for study of peripheral and central 5-HT receptors in man.

Binding Sites↗
PubMed1984

Decreased platelet 3H-imipramine binding sites in classical migraine.

Patients with classical migraine investigated between attacks had significantly fewer platelet 3H-imipramine binding sites than control subjects and this finding was more marked in males than in females. There was no abnormality of binding characteristics of platelet 5-hydroxytryptamine receptors or of platelet alpha 2-adrenoceptors. Because the reduced 3H-imipramine binding capacity was found in classical migraineurs who were investigated between attacks, it may reflect a predisposition to migraine rather than being a consequence of attacks.

Blood Platelets↗
PubMed1983

Inhibition of 5-hydroxytryptamine-mediated behaviour by the putative 5-HT2 antagonist pirenperone.

The effect of pirenperone, a putative 5-HT2 receptor antagonist, on various 5-HT-mediated behavioural responses has been examined. The head twitch response in mice, induced by administration of carbidopa (25 mg/kg) followed by 5-hydroxytryptophan (5-HTP) (200 mg/kg), was inhibited in a dose-dependent manner by pirenperone, with an ED50 of 76 micrograms/kg. The appearance of head weaving, forepaw treading and hind-limb abduction, which followed the administration of tranylcypromine (5 mg/kg) plus L-tryptophan (100 mg/kg) or quipazine (50 mg/kg) to rats, was also inhibited by pretreatment with pirenperone (100 micrograms/kg). Pirenperone did not alter the rate of 5-HT synthesis in the rat brain. Whilst pirenperone (100 micrograms/kg) did decrease methamphetamine-induced locomotor activity in rats, a dose of haloperidol producing a similar inhibition of this response did not alter the 5-HT-mediated behaviour. It is suggested, therefore, that the currently used 5-HT-induced behavioural models are 5-HT2 receptor-mediated.

5-Hydroxytryptophan↗