Binding studies with [3H]cis-methyldioxolane in different tissues. Under certain conditions [3H]cis-methyldioxolane labels preferentially but not exclusively agonist high affinity states of muscarinic M2 receptors.
Special conditions--tricine buffer containing Ca2+ and Mg2+, 22 degrees C (TCM)--allow to label a much higher proportion of muscarinic receptors by [3H]cis-methyldioxolane (CD) than hitherto described (Vickroy et al. 1984a). Taking the maximum number of binding sites, Bmax, of [3H]QNB as 100%, Bmax of [3H]CD amounts to 83% in the rat heart instead of the reported 17%, 33% in the cerebral cortex instead of 6%, 20% in hippocampus and 55% in pons/medulla. In the salivary glands specific binding was negligible. The affinities of a number of muscarinic agonists and antagonists to [3H]CD and [3H]QNB binding sites in different tissues of the rat are compared. Apparent affinities of agonists are much higher in the [3H]CD system, affinities of antagonists are slightly higher in the [3H]QNB system. In both assay systems receptors of heart and pons/medulla membranes seem to have similar drug specificity. They differ somewhat from those in the cortex. Receptors in the salivary glands, however, seem to be completely different from those in the other three tissues. In the heart [3H]CD binding can be abolished almost completely by GppNHp. In the cortex about half of the [3H]CD binding is susceptible to GppNHp. The reduction of binding in the cortex is due to a change in Bmax and not in the dissociation constant KD. Competition of unlabelled pirenzepine with [3H]CD: In heart and pons/medulla only low affinity sites for pirenzepine (M2-receptors) are labelled by [3H]CD.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D004148:Dioxolanes / Q000378:metabolism*; D004149:Dioxoles / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010277:Parasympathomimetics / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism; D013237:Stereoisomerism
D004148:Dioxolanes; D004149:Dioxoles; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D006165:Guanylyl Imidodiphosphate; C024310:2-methyldioxolane; D011813:Quinuclidinyl Benzilate