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.
Antagonism of striatal muscarinic receptors inhibiting dopamine D-1 receptor-stimulated adenylyl cyclase activity by cholinoceptor antagonists used to treat Parkinson's disease
OLIANAS, MARIA CONCETTA;ONALI, PIER LUIGI
1996-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.