The ability of the muscarinic agonist, carbachol, to overcome increases in tension and in cAMP produced in response to the adenylate cyclase activator, forskolin, in rabbit papillary muscles was measured. Forskolin alone increased cAMP levels to a much greater extent than did a concentration of isoproterenol that produced an equivalent increase in tension. Carbachol completely overcame the increase in tension, while having no effect on the increase in cAMP, produced by forskolin. The response to carbachol was associated with a significant increase in cGMP levels. It appears that carbachol may block the inotropic response to forskolin by antagonizing the effects of forskolin-induced increases in cAMP.
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