Pharmacological and molecular characterization of muscular cholecystokinin receptors in the human lower oesophageal sphincter.

In vitro cholecystokinin (CCK) contracts the human lower oesophageal sphincter by stimulating muscular receptors. The aim of this study was to characterize the muscular CCK receptor subtypes in the human lower oesophageal sphincter. Twenty-five circular strips from six patients were studied. RNA was extracted, reverse transcribed, and cDNAs were amplified with primers for human CCK-A and B receptors. The potency of the contraction induced by CCK-8, desulphated CCK-8, and gastrin-I, and the effect of the CCK-A (loxiglumide and SR 27897) and the CCK-B (YM022 and L-365 260) specific receptor antagonists were compared. Both CCK-A and CCK-B receptor mRNAs were found in functional lower oesophageal sphincter strips. The potency of the CCK-8 concentration-dependent contraction was two and three orders of magnitude higher than that of desulphated CCK-8 and gastrin-I, respectively. The CCK-8-induced contraction was blocked by the CCK-A receptor antagonists loxiglumide (IC50 11 micromol L-1) and SR 27897 (IC50 74 nmol L-1) but not by CCK-B receptor antagonists (1 micromol L-1). Our data suggest that, although the human lower oesophageal sphincter expresses both CCK-A and CCK-B receptors, the contractile effect of CCK-8 on the circular muscle is mainly due to the activation of CCK-A receptors.