Differential Affinities of AF-DX 116, Atropine and Pirenzepine for Muscarinic Receptors of Guinea Pig Gastric Fundus, Atria and Urinary Bladder: Might Atropine Distinguish among Muscarinic Receptor Subtypes?

Abstract

The pA₂ values and the Schild plots of the antimuscarinic drugs AF-DX 116, atropine and pirenzepine for muscarinic receptors of isolated guinea pig gastric fundus (acid secretion) and atrial and urinary bladder preparations (contractile force) obtained from the same animals were calculated against bethanechol as the agonist. The antimuscarinic drugs concentration-dependently shifted the concentration-response curves to bethanechol to the right without any change in the maximum response. The analysis of data based on Schild plots was consistent with a simple competitive antagonism, since regression slopes did not differ significantly from unity. The pA₂ values indicated a significantly higher affinity of AF-DX 116 and atropine for atrial muscarinic receptors with respect to those of the gastric mucosa or urinary bladder. By contrast, in the case of pirenzepine the pA₂ values for the three tissues did not differ significantly. These results suggest that each examined tissue apparently contains homogeneous population of acetylcholine muscarinic (M₂) receptors. The pA₂ values found for AF-DX 116 and atropine suggest, however, that the putative M₂ subtype of atrial muscarinic receptor differs from both those of the gastric fundus and those of the urinary bladder.

Muscarinic Agonists and Antagonists: Effects on Gastrointestinal Function

“…Muscarinic agonist-induced contraction of the longitudinal muscle of the ileum (Lambrecht et al 1989;Eglen and Harris 1993;Thomas et al 1993), colon Ehlert 1998, 1999b), esophagus (Kamikawa et al 1985;, and stomach (Del Tacca et al 1990) is competitively inhibited by antagonists with pK B values that are indicative of an M 3 response. The contractile response of the ileum and colon and field-stimulated contraction of the ileum is slightly increased or unaffected by pertussis toxin treatment Thomas and Ehlert 1994;Sawyer and Ehlert 1999a, b).…”