Relationship between the contractile responses and their coupling second messenger systems for muscarinic drugs in the guinea-pig ileal longitudinal muscle

Abstract

The relationship between the contractile responses and their coupling second messenger systems such as IPs formation, release of intracellular Ca2+ and Ca2+ influx in the presence of muscarinic agonists and antagonists in guinea-pig ileal longitudinal muscles was examined by using several pharmacological methods. The pD2 for carbachol-induced contraction in the presence of extracellular Ca2+ was greater than that obtained for carbachol in the absence of extracellular Ca2+, which was, in turn, greater than that for carbachol-induced stimulation of IP formation. The pD2-values of oxotremorine and pilocarpine were also higher for the contraction occurring in the presence of extracellular Ca2+ and for the normal contractions than for those of the contraction occurring when Ca2+ was deleted from medium and the IPs formation. In normal contraction and in contraction occurring in the presence of extracellular Ca2+, pilocarpine and oxotremorine were full agonists or highly efficacious partial agonists, while in contraction occurring when Ca2+ was removed from the medium and in IPs formations, they behaved as partial agonists with lower efficacy. However, the dissociation constants for muscarinic agonists and selective or non-selective antagonists were similar under the experimental conditions used. These results suggest that the muscarinic receptors, coupled to each of the different second messenger systems in the ileum, are of the same type.