Differences and similarities in muscarinic receptors of rat heart and retina: effects of agonists, guanine nucleotides, and N-ethylmaleimide.
Muscarinic receptor stimulation inhibits cyclic AMP formation in rat atria but not in retina. We compared the properties of the muscarinic receptors in rat atrial and retinal membranes using the antagonist [3H]quinuclidinyl benzilate. In both atria and retina there is a single binding site for antagonists, while agonists appear to interact at two classes of binding sites. Muscarinic receptors in atria and retina have the same apparent affinities for several antagonists and for a series of muscarinic agonists. In both tissues N-ethylmaleimide decreases agonist affinity for the high-affinity binding sites. Muscarinic receptors in atria and retina differ, however, in several properties relating to the proportions of high- and low-affinity agonist sites. First, guanine nucleotides markedly increase the proportion of low-affinity binding sites in atria, but not in retina. Second, for all agonists there are fewer high-affinity binding sites in retina. Third, the "partial agonist" pilocarpine appears to interact with two classes of binding sites in atria, but with only a single class of sites in retina. Our data suggest that muscarinic receptors that inhibit cyclic AMP formation and those that do not share common properties that determine receptor affinity for agonists and classic antagonists. The differences between these receptors are manifest, however, in the effects of guanine nucleotides and the ability of agonists, especially those of low efficacy, to affect the proportion of high- and low-affinity sites and to effect a biological response.
D000818:Animals; D001667:Binding, Competitive; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology*; D006150:Guanine Nucleotides / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010862:Pilocarpine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*
D006150:Guanine Nucleotides; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D000242:Cyclic AMP; D005033:Ethylmaleimide