Dopamine receptors modulating [3H]acetylcholine release in slices of the cat caudate: effects of (-)-N-(2-chloroethyl)-norapomorphine.
(-)-N-(2-Chloroethyl)-norapomorphine [-)-NCA) inhibited in a concentration-dependent manner the electrically evoked [3H]acetylcholine release in slices of cat caudate. The inhibition by (-)-NCA was reversible and antagonized by the benzamide neuroleptic S-sulpiride. Although (-)-NCA is an irreversible antagonist at some behaviorally relevant postsynaptic dopamine receptors, its effect as an agonist on dopamine receptors modulating [3H]acetylcholine release strongly resembles its action on presynaptic dopamine autoreceptors modulating [3H]dopamine release. Our results suggest that the dopamine receptor modulating [3H]acetylcholine release may not be an appropriate in vitro model for those behaviorally relevant postsynaptic dopamine receptors which are antagonized by (-)-NCA. It is more likely that it conforms to the characteristics of presynaptic release-modulating dopamine autoreceptors. The agonistic action of (-)-NCA at presynaptic dopamine receptors, in contrast to the irreversible antagonism of some postsynaptic dopamine receptors by (-)-NCA, should be interpreted with caution. Evidence is presented which suggests that (-)-NCA breaks down in solution into (-)-N-(2-hydroxylethyl)-norapomorphine [-)-NHA). Since (-)-NHA is an agonist at presynaptic dopamine receptors, this physicochemical breakdown product may be partly responsible for the apparent agonistic properties of (-)-NCA under our in vitro conditions.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001060:Aporphines / Q000378:metabolism / Q000494:pharmacology*; D002415:Cats; D002421:Caudate Nucleus / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D066298:In Vitro Techniques; D008297:Male; D011954:Receptors, Dopamine / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology; D014316:Tritium
D001060:Aporphines; D011954:Receptors, Dopamine; D014316:Tritium; C025935:chloroethylnorapomorphine; D013469:Sulpiride; D000109:Acetylcholine