Prejunctional muscarinic (M₁)‐receptor interactions on guinea‐pig ileum: lack of effect of cisapride

Abstract

1Cisapride stimulates gastrointestinal motility, probably by enhancing the release of acetylcholine from myenteric nerve endings. Such an effect could be mediated via presynaptic muscarinic (Ml)-receptors. Our aim was to determine whether cisapride could antagonize the inhibitory effects of a M1-agonist, or mimic the effects of a M,-antagonist, pirenzepine.2 Longitudinal segments were suspended in Krebs solution (95% 02, 5% CG2, 37.5C) for isometric tension recording (preload 1 g) during electrical transmural stimulation (0.1 Hz, 1 ms, sub-or supramaximal current). 3 McN-A-343 (2.0 x 10-6M) reduced the contractile response to supramaximal stimulation (EC50 = 1.6 x 10-6 M), but had no effect on the contractions induced by exogenous acetylcholine. 4 The inhibitory effect of McN-A-343 on the contractile response to electrical stimulation could be reversed by pirenzepine (ECQ0 = 1.6 x 10-8M) but not by atropine. At these concentrations pirenzepine itself did not modify the contractile response to electrical stimulation. However, at 50 times higher concentrations pirenzepine inhibited the response to electrical stimulation as well as the response to exogenous acetylcholine (ECQ0 = 8.5 x 10-7 M).

Investigation of the role of 5‐HT3 and 5‐HT4 receptors in ascending and descending reflexes to the circular muscle of guinea‐pig small intestine

“…However, these receptors can be activated by adding exogenous 5-HT or its agonists (Craig & Clarke, 1991). Cisapride, for example, in the present experiments facilitated the ascending excitatory reflex, consistent with its prokinetic actions (Schuurkes et al, 1988;Tonini et al, 1989). This effect of cisapride can be converted to a significant depression of the ascending excitatory reflexes by SDZ 205-557.…”

Immunohistochemical localisation of cholinergic muscarinic receptor subtype 1 (M1r) in the guinea pig and human enteric nervous system

“…This was expected based on physiological and pharmacological studies (Schuurkes et al, 1988;Kawashima et al, 1990;Dietrich and Kilbinger, 1995). We also found M1r-IR nerve fibres in the circular and longitudinal muscle in both species, which is in agreement with a number of functional studies describing prejunctional M1rs in circular and longitudinal muscle (Dietrich and Kilbinger, 1995).…”

Interaction of selective compounds with muscarinic receptors at dispersed intestinal smooth muscle cells

“…It is known that McN-A-343 inhibits electrically-stimulated contractions of guinea-pig ileum (Schuurkes et al, 1988) by selectively interacting with neuronal MI-receptors. has been reported to act as full agonist on taenia caeci muscarinic receptors (Eglen et al, 1987) and as a partial agonist on guinea-pig ileum (Van Rossum, 1962).…”

“…Accordingly, a pirenzepine-sensitive inhibitory neuronal effect of McN-A-343 has been described on electricallyinduced contractions of guinea-pig ileum (Schuurkes et al, 1988). A simultaneous direct motor activity in response to non competitively antagonized by antimuscarinic drugs (atropine, 4-DAMP, methoctramine and pirenzepine), has been observed on guinea-pig ileum longitudinal muscle strips (Impicciatore et al, unpublished data).…”