Subclassification of atrial and intestinal muscarinic receptors of the rat—direct binding studies with agonists and antagonists

Abstract

1 Although extensively investigated, the extent of differences between receptors mediating negative inotropic and chronotropic responses is still unclear. In the present study atrial and intestinal muscarinic receptors were identified by [3H]-N-methyl-scopolamine ([3H]-NMS) binding and the affinities of some presumably inotropy-or chronotropy-selective agonists and several antagonists determined. 2 All the agonists tested showed similar affinity for right and left atrial receptors. Accepting an affinity difference of 0.4 log units as experimental error, none of the agonists tested was selective for either atrium. 3 Affinity differences of the cardioselective antagonists himbacine, AF-DX 116 and methoctramine and the Ml-selective antagonist dicyclomine for right and left atrial muscarinic receptors were also minimal (less than 2 fold selective). When compared to intestinal receptors, AF-DX 116 was 3 to 4 fold, methoctramine 10 to 13 fold selective and himbacine and dicyclomine non-selective. 4 These data provide evidence for differences between atrial and intestinal but not between right and left atrial muscarinic receptors.

Increased function of inhibitory neuronal M2 muscarinic receptors in trachea and ileum of diabetic rats

“…This suggests that post‐junctional M 2 muscarinic receptors play a role in mediating carbachol‐induced contraction of ileal smooth muscle. Receptor‐binding studies have shown that the majority of muscarinic receptors on ileal smooth muscle are M 2 , with a smaller proportion of M 3 receptors (Brunner, 1989; Lazareno & Roberts, 1989; Kurjak et al ., 1999). Despite the preponderance of M 2 receptors in the ileum, the contractile response to muscarinic agonists is largely due to M 3 receptor activation.…”