Autoradiographic localisation of muscarinic receptors in guinea-pig intestine: Distribution of high and low affinity agonist binding sites

Abstract

Muscarinic receptors mediate a variety of intestinal functions including smooth muscle contraction, ganglionic transmission and water and electrolyte secretion. In this study, we have used [ 3H]quinuclidinyl benzilate ([ 3H]QNB) in an in vitro autoradiographic method to map the distribution of muscarinic receptors in guinea-pig ileum, colon and caecum. In addition, the relative distribution of low and high affinity agonist binding sites was assessed by the addition of the muscarinic agonist, carbachol, to selectively inhibit the binding of [ 3H]QNB to the high affinity sites. Although quantitative differences existed, the overall distribution of muscarinic receptors was similar in the 3 regions of intestine examined. Autoradiograph grains were found distributed over the myenteric and sub-mucous plexuses, the longitudinal and circular muscle layers and in the case of the colon, the muscularis mucosa. The inclusion of carbachol demonstrated that a greater proportion of high affinity sites were associated with the musculature than with the enteric plexuses. These findings are discussed in relation to the role of muscarinic mechanisms in intestinal motility and secretion.