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P M Whitaker

Publications and source records attributed to P M Whitaker.

5 recordsLinked to original sources
PubMed1979

Selective labeling of apomorphine receptors by 3H-LSD.

There are at least two types of dopamine receptors: the 3H-dopamine or 3H-apomorphine receptor (with high or nM affinity for dopamine), and the 3H-neuroleptic receptor (with low or microM affinity for dopamine). While 3H-LSD can label the 3H-neuroleptic receptor, this study was done in order to label the 3H-apomorphine/dopamine receptor site. In the presence of excess phentolamine, serotonin and spiperone (to preclude binding to alpha-adrenergic, serotonergic and neuroleptic receptors, respectively) similar concentrations of dopaminergic drugs inhibited the binding (to calf caudate) of 3H-LSD and 3H-apomorphine. This is compatible with the concept that the 3H-apomorphine/dopamine receptor and the 3H-neuroleptic/dopamine receptor are separate.

Animals↗
PubMed1978

High-affinity 3H-serotonin binding to caudate: inhibition by hallucinogens and serotoninergic drugs.

The specific binding of 3H-serotonin to calf caudate homogenate was studied. The dissociation constant was 2nM and the number of specific sites was 14fmoles/mg protein. Of many drugs tested, inhibition of specific 3H-serotonin binding occurred almost exclusively with serotonin agonists and antagonists. The concentrations for 50% inhibition of 3H-serotonin binding by serotonergic agonists follow: bufotenin, 6nM; 5-methoxytryptamine, 12 nM; psilocin, 35nM; dimethyltryptamine, 220 nM; and tryptamine, 270 nM. The concentrations for the antagonists were: LSD 9.5 nM; methysergide 16nM and metergoline 25nM.

Animals↗
PubMed1978

Selective labeling of serotonin receptors by d-[3H]lysergic acid diethylamide in calf caudate.

Since it was known that d-lysergic acid diethylamide (LSD) affected catecholaminergic as well as serotoninergic neurons, the objective in this study was to enhance the selectivity of [3H]LSD binding to serotonin receptors in vitro by using crude homogenates of calf caudate. In the presence of a combination of 50 nM each of phentolamine (added to preclude the binding of [3H]LSD to alpha-adrenoceptors), apomorphine, and spiperone (added to preclude the binding of [3H]LSD to dopamine receptors), it was found by Scatchard analysis that the total number of [3H]LSD sites went down to 300 fmol/mg, compared to 1100 fmol/mg in the absence of the catecholamine-blocking drugs. The IC50 values (concentrations to inhibit binding by 50%) for various drugs were tested on the binding of [3H]LSD in the presence of 50 nM each of apomorphine (A), phentolamine (P) and spiperone (S). With this combination, the IC50 for serotonin was 35 nM (compared to 1000 nM without it), indicating that [3H]LSD had become considerably more selectively displaceable by serotonin under these conditions whereas the effects of norepinephrine and dopamine on [3H]LSD binding were eliminated. Various ergots had approximately equal IC50 values against [3H]serotonin and [3H]LSD but tryptamines were much more selective against [3H]serotonin; the data may indicate the existence of the two types of serotonin receptors.

Animals↗
PubMed1978

Dopamine receptors in the central nervous system.

Dopamine receptors in the central nervous system can be studied by measuring the specific binding of [3H]dopamine, [3H]haloperidol, d-[3H]LSD, [3H]dihydroergocryptine or [3H]apomorphine. The receptors are stereoselectively blocked by +)-butaclamol, a neuroleptic. All neuroleptics inhibit the specific binding of [3H]haloperidol in relation to their clinical potencies. The radioligand that desorbs most slowly from the receptor is [3H]apomorphine, thus making it a reliable ligand for dopamine receptors. Dopamine agonists that compete for [3H]apomorphine binding do so at concentrations that correlate with their potency in stimulating striatal adenylate cyclase. Structure-activity analysis, using [3H]apomorphine, confirms that the active dopamine-mimetic conformation is the beta rotamer of dopamine. Prolonged exposure in vitro of caudate homogenate to high concentrations of dopamine leads to increased binding of [3H]apomorphine or [3H]haloperidol, suggesting receptor "sensitization." Chronic haloperidol treatment of rats leads to an increased number of dopamine/neuroleptic receptors in the striatum, but a decrease in the pituitary.

Adenylyl Cyclases↗