Enhancement of guinea‐pig intestinal peristalsis by blockade of muscarinic M1‐receptors

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Abstract
1 The effects of pirenzepine and hyoscine on the peristaltic reflex were investigated in the guinea-pig isolated small intestine. Peristalsis was induced by raising the intraluminal pressure and the volume of fluid propelled was taken as a measure of the efficiency of peristaltic activity. 2 Low concentrations of pirenzepine (0.1-1 nm) and of hyoscine (0.01 nm) significantly enhanced peristalsis, whereas larger concentrations of both drugs caused inhibition. Pirenzepine was about 6 times less potent than hyoscine in increasing peristalsis, but was about 100 times less potent in inhibiting it. 3 Neither tolazoline (1 μm) nor naloxone (0.3 μm) affected the stimulatory action of pirenzepine on peristalsis. 4 Bicuculline increased the efficiency of peristalsis at concentrations of 1 μm and 10 μm; at 10 nm, bicuculline reduced significantly the increase of peristalsis by pirenzepine. γ-Aminobutyric acid (GABA) did not affect peristaltic activity, but the stimulatory effect of pirenzepine was abolished in the presence of 100 μm GABA. 5 The results indicate that activation of neuronal M1-receptors causes inhibition of small intestinal peristalsis. Bicuculline-sensitive ‘GABAergic’ synapses are probably involved in this inhibition.