Antagonism of striatal muscarinic receptors inhibiting dopamine D1 receptor-stimulated adenylyl cyclase activity by cholinoceptor antagonist used to treat Parkinson's disease.
A number of cholinoceptor antagonists used in the treatment of Parkinson's disease were examined for their ability to antagonize either the muscarinic receptor-mediated inhibition of dopamine D1 receptor-stimulated adenylyl cyclase or the muscarinic receptor-mediated stimulation of [3H]-inositol phosphates ([3H]-IPs) formation in rat striatal membranes. The drugs were found to block the receptors inhibiting adenylyl cyclase activation with high affinity and more potently than those stimulating [3H]-IPs formation. Moreover, their rank order of potencies for the former effect showed good correlation with their clinical efficacies. These data suggest that the blockade of the muscarinic receptor-mediated inhibition of striatal dopamine D1 receptor activation may be one of the mechanisms by which cholinoceptor blocking drugs exert their antiparkinsonian effect.
Olianas
M C
MC
Department of Neurosciences, University of Cagliari, Italy.
Onali
P
P
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D002217:Carbachol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003342:Corpus Striatum / Q000201:enzymology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D000978:Antiparkinson Agents; D001552:Benzazepines; D018491:Dopamine Agonists; D007295:Inositol Phosphates; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D017447:Receptors, Dopamine D1; D011976:Receptors, Muscarinic; C071262:SK&F 82958; D002217:Carbachol; D000262:Adenylyl Cyclases