Evidence for the presence of cholinergic muscarinic receptors negatively linked to adenylate cyclase in the iris-ciliary body.

Adenylate cyclase activity can be stimulated in the rabbit iris-ciliary body directly by forskolin or through receptor-mediated mechanisms by vasoactive intestinal peptide (VIP) and the ?-adrenoreceptor agonists isoproterenol and salbutamol. Increases in the level of c-AMP observed following application of forskolin, isoproterenol and VIP are decreased by carbachol in a dose-dependent manner. The carbachol response is blocked by pertussis toxin and is insensitive to the phosphodiesterase inhibitor theophyline suggesting the involvement of a Gi-protein. Carbachol attenuation of elevated c-AMP levels can be inhibited by the muscarinic antagonist atropine but not by the specific muscarinic receptor antagonist pirenzepine. This is in contrast to carbachol stimulation of inositol phosphate accumulation, where both atropine and pirenzepine inhibit the muscarinic response. Thus there exist two distinct muscarinic receptors in the iris-ciliary body, one linked to adenylate cyclase and the other to the hydrolysis of phosphoinositides.