Dissociation between the presynaptic dopamine-sensitive adenylate cyclase and [3H]spiperone binding sites in rat substantia nigra.
[3H]Spiperone binding sites and the dopamine-sensitive adenylate cyclase were measured in rat substantia nigra (s. nigra) 7 or 14 days after various lesions. Hemisections, which resulted in a 66% decline in tyrosine hydroxylase and cyclic nucleotide phosphodiesterase and a 73% decrease in glutamate decarboxylase, led to a 50% decrease in [3H]spiperone binding and to the almost complete disappearance of the dopamine-sensitive adenylate cyclase from the s. nigra on the lesioned side. 6-Hydroxydopamine injection into the s. nigra, which depleted tyrosine hydroxylase activity within the s. nigra by 85%, while leaving phosphodiesterase unaffected, resulted in a 40% decrease in [3H]spiperone binding but no change in the dopamine-sensitive adenylate cyclase. Intrastriatal injections of kainic acid did not alter tyrosine hydroxylase activity in the s. nigra, but decreased both glutamate decarboxylase (54%) and phosphodiesterase (68%); [3H]spiperone binding was unaffected by this lesion while the dopamine-sensitive adenylate cyclase was greatly reduced (50-75%). These results suggest that within the s. nigra the dopamine receptor binding sites as defined using [3H]spiperone are located on dopamine neurones while the dopamine-sensitive adenylate cyclase is located presynaptically on striatonigral nerve terminals.
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002090:Butyrophenones / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006892:Hydroxydopamines / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology*; D013764:Tetrahydronaphthalenes / Q000378:metabolism / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002090:Butyrophenones; D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D013134:Spiperone; D014446:Tyrosine 3-Monooxygenase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D005968:Glutamate Decarboxylase; D000262:Adenylyl Cyclases; D007608:Kainic Acid; D004298:Dopamine