Cisapride (Ci) stimulates lower esophageal sphincter pressure (LESP). This study aims to test whether the effect of Ci on LES in vivo is still present if LES is relaxed by atropine (Atr) and nifedipine (Nife) prior to the administration of Ci. LESP was continuously recorded by manometry in 6 mongrel dogs with esophageal fistulae. Ci was given as an intravenous bolus following either Atr (40 µg/kg i.v.) or Nife (20 mg subl.) at the time of maximal LESP decrease (5/15 min later). Basal LES values ranged between 24.5 ± 2.5 mm Hg (Atr group) and 23.8 ± 3.9 mm Hg (Nife group). Following Atr, LESP decreased to a minimal value of 7.0 ± 0.5 mm Hg; after Nife LESP decreased to a minimal value of 12.3 ± 2.0 mm Hg. Additional administration of Ci was not able to reincrease LESP. We conclude that the action of Ci on LES cannot take place if (1) muscarinergic receptors are blocked by Atr and (2) the Ca2+ activation system is blocked by Nife. Our results suggest that the action of cisapride on LES, as its action on gastrointestinal smooth muscle cells, is mediated by postsynaptic enhancement of acetylcholine release.

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