Enhancement of guinea-pig intestinal peristalsis by blockade of muscarinic M1-receptors.

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 microM) nor naloxone (0.3 microM) affected the stimulatory action of pirenzepine on peristalsis. 4. Bicuculline increased the efficiency of peristalsis at concentrations of 1 microM and 10 microM; at 10 nM, bicuculline reduced significantly the increase of peristalsis by pirenzepine. gamma-Aminobutyric acid (GABA) did not affect peristaltic activity, but the stimulatory effect of pirenzepine was abolished in the presence of 100 microM 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.