Muscarinic inhibition of hippocampal and striatal adenylyl cyclase is mainly due to the M(4) receptor.
The five muscarinic acetylcholine receptors (M(1)-M(5)) are differentially expressed in the brain. M(2) and M(4) are coupled to inhibition of stimulated adenylyl cyclase, while M(1), M(3) and M(5) are mainly coupled to the phosphoinositide pathway. We studied the muscarinic receptor regulation of adenylyl cyclase activity in the rat hippocampus, compared to the striatum and amygdala. Basal and forskolin-stimulated adenylyl cyclase activity was higher in the striatum but the muscarinic inhibition was much lower. Highly selective muscarinic toxins MT1 and MT2-affinity order M(1) > or = M(4) >> others-and MT3-highly selective M(4) antagonist-did not show significant effects on basal or forskolin-stimulated cyclic AMP production but, like scopolamine, counteracted oxotremorine inhibition. Since MTs have negligible affinity for M(2), M(4) would be the main subtype responsible for muscarinic inhibition of forskolin-stimulated enzyme. Dopamine stimulated a small fraction of the enzyme (3.1% in striatum, 1.3% in the hippocampus). Since MT3 fully blocked muscarinic inhibition of dopamine-stimulated enzyme, M(4) receptor would be responsible for this regulation.
Sánchez
Gonzalo
G
Instituto de Biología Celular & Neurociencia "Prof. Eduardo De Robertis", Facultad de Medicina, Universidad de Buenos Aires-CONICET, Paraguay 2155, 2Do piso, 1121 Buenos Aires, Argentina.
Colettis
Natalia
N
Vázquez
Pablo
P
Cerveñansky
Carlos
C
Aguirre
Alejandra
A
Quillfeldt
Jorge A
JA
Jerusalinsky
Diana
D
Kornisiuk
Edgar
E
D000262:Adenylyl Cyclases / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology*; D010095:Oxotremorine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043588:Receptor, Muscarinic M4 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D043588:Receptor, Muscarinic M4; D005576:Colforsin; D010095:Oxotremorine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D004298:Dopamine