MUSCARINIC RECEPTOR-MEDIATED PHOSPHOINOSITIDE HYDROLYSIS IN THE RAT RETINA

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  • 1 August 1988
    • journal article
    • research article
    • Vol. 246  (2) , 553-557
Abstract
In this report, muscarinic receptor-mediated phosphoinositide (PI) hydrolysis is characterized pharmacologically in the rat retina. In the presence of eserine, acetylcholine (ACh) elicited a concentration-dependent increase in inositol monophosphate with a calculated EC50 of about 2.8 .mu.M. Maximum increase was achieved with about 100 .mu.M ACh. Cholinergic receptor agonists stimulated phospholipase C-mediated hydrolysis of PI with the following rank order of potency: ACh = oxotremorine > McN-A-343 > bethanecol > arecoline = carbachol > muscarine. Oxotremorine analogs stimulated PI hydrolysis with the following rank order of potency: ACh = oxotremorine = oxotremorine-2 > oxotremorine-M oxotremorine-4. Carbachol-mediated PI hydrolysis was blocked by atropine and by the putatively selective muscarinic type 1 (M1) receptor antagonist, pirenzepine, with apparent Ki values of 0.1 and 1.0 nM, respectively. In contrast, the selective muscarinic type 2 (M2) antagonists, gallamine and AF-DX 116, failed to inhibit the action of carbachol. These findings demonstrate that stimulation of muscarinic receptors in the rat retina leads to PI hydrolysis and that these receptors appear to be M1 cholinergic receptors.