Muscarinic cholinergic inhibition of adenylate cyclase in the rabbit iris-ciliary body and ciliary epithelium.
The effects of cholinergic agents on hormone-stimulated cyclic AMP (cAMP) accumulation were investigated in iris-ciliary body segments, excised ciliary processes, and isolated ciliary epithelium from albino rabbit eyes. In all three tissue preparations, the cholinergic agonist carbamylcholine markedly inhibited the stimulation of cAMP biosynthesis by vasoactive intestinal peptide VIP--a potent activator of nonpigmented ciliary epithelial adenylate cyclase. Carbamylcholine also attenuated cAMP increases mediated by isoproterenol, prostaglandin E2, and forskolin. The effects of carbamylcholine on VIP-induced cAMP synthesis were concentration dependent (EC50 = 23 nM), mimicked by selective muscarinic cholinergic agonists (oxotremorine, pilocarpine), and antagonized by atropine. Carbamylcholine- and clonidine-mediated inhibition of VIP-stimulated cAMP accumulation in ciliary processes were nonadditive, indicating that inhibitory muscarinic and alpha 2-adrenergic receptors coexist on VIP-responsive target cells. These findings suggest that the cholinergic system may have a direct role in modulation of ciliary epithelial adenylate cyclase and aqueous humor secretion.
Jumblatt
J E
JE
Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Kentucky Lions Eye Research Institute 40202.
North
G T
GT
Hackmiller
R C
RC
D000255:Adenosine Triphosphate / Q000378:metabolism; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002924:Ciliary Body / Q000187:drug effects* / Q000201:enzymology; D000242:Cyclic AMP / Q000096:biosynthesis; D004347:Drug Interactions; D004848:Epithelium; D005260:Female; D007498:Iris / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D011817:Rabbits; D013566:Sympathomimetics / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D010276:Parasympatholytics; D010277:Parasympathomimetics; D013566:Sympathomimetics; D014660:Vasoactive Intestinal Peptide; D000255:Adenosine Triphosphate; D002217:Carbachol; D000242:Cyclic AMP