Enhancing effect of dopamine blockers on evoked acetylcholine release in rat striatal slices: a classical D-2 antagonist response?
The effects of chlorpromazine, pipotiazine, haloperidol, domperidone, sulpiride and SCH 23390 on the potassium-evoked release of [3H]acetylcholine [( 3H]ACh) were studied in rat striatal slices. All 5 dopamine (DA) antagonists with D-2 blockade efficacy induced an increase of [3H]ACh release whereas the specific D-1 antagonist SCH 23390 was devoid of significant effects. The maximal effect (about 100% increase) was obtained with haloperidol, pipotiazine and sulpiride but not with domperidone and chlorpromazine. Interestingly, sulpiride was found to exert an unexpected marked potency. The comparison of the activities of the 6 compounds on evoked ACh release to their affinities for D-2 receptors [( 3H]N-propylnorapomorphine binding sites) indicates that the pharmacological profile of the dopamine receptor implicated in the regulation of ACh release cannot be superimposed on that of the classical D-2 receptor. Participation of DA presynaptic receptors could however explain the differences in efficacy observed with the compounds studied.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects*; D004294:Domperidone / Q000494:pharmacology; D018492:Dopamine Antagonists; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010640:Phenothiazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D010640:Phenothiazines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D004294:Domperidone; D013469:Sulpiride; D006220:Haloperidol; D000109:Acetylcholine; D002746:Chlorpromazine