Muscarinic stimulation of adenylate cyclase activity of rat olfactory bulb. I. Analysis of agonist sensitivity.
In rat olfactory bulb, stimulation of muscarinic receptors activates adenylate cyclase. In the present study we have examined a variety of muscarinic receptor stimulants to characterize the agonist profile of this response. Analysis of agonist concentration-response curves revealed the following rank order of potency: oxotremorine-M greater than oxotremorine greater than BM5 greater than acetylcholine greater than carbachol = methacholine greater than (+/-)muscarine greater than arecoline greater than pilocarpine greater than RS 86 greater than McN-A-343 greater than bethanechol. Acetylcholine, oxotremorine-M, carbachol, (+/-)muscarine and metacholine behaved as full agonists, whereas the other stimulants displayed lower efficacies. The slope values of the concentration-response curves were close or equal to 1, except those of the carbachol and pilocarpine curves, which showed values significantly lower than 1. Moreover, the slope of the pilocarpine curve was differentially changed by the M1 antagonist pirenzepine and the M2 antagonist AF-DX 116. The agonist profile of the muscarinic stimulation of adenylate cyclase in the olfactory bulb correlated well with that exhibited by the muscarinic inhibition of the enzyme activity in the striatum, suggesting that the two responses are mediated by a similar receptor subtype. Sodium ion modulated the agonist affinity for both adenylate cyclase-coupled receptor systems.
Department of Neurosciences, University of Cagliari, Italy.
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D000109:Acetylcholine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004347:Drug Interactions; D008297:Male; D018727:Muscarinic Antagonists; D009830:Olfactory Bulb / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D010862:Pilocarpine / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology; D013268:Stimulation, Chemical
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D010890:Pirenzepine; D012964:Sodium; D000262:Adenylyl Cyclases; D000109:Acetylcholine; C048593:otenzepad