Pharmacological characterization of cholecystokinin receptors mediating contraction of human gallbladder and ascending colon

Cholecystokinin (CCK) produces contractions of gallbladder and colon in a number of different species. Although the effects of CCK on the human gallbladder are relatively well documented, the CCK receptors in the human colon have not been clearly characterised. Therefore, in this study, the CCK receptors in the human gallbladder and colon were compared using pharmacological techniques. Contraction of specimens of the human tissue was measured using in vitro organ bath bioassay. The effect of selective concentrations of CCK1 and CCK2 receptor antagonists (L-364,718 and JB93182, respectively) was determined on agonist concentration-effect(E/[A]) curves obtained by cumulative dosing with sulphated CCK. The CCK1 antagonist L-364,718 produced a rightward shift of the CCK-8S [E/[A] curve in the human gallbladder (pA(2) = 9.15 +/- 0.26) and ascending colon (pA(2) = 9.20 +/- 0.33). In both tissues, the CCK2 receptor antagonist, JB93182, had no effect on the CCK E/[A] curves. In addition, in the colon, pentagastrin responses were inhibited by L-364,718 but unaffected by JB93182. These data indicate that the CCK-induced contraction of the human colon and gallbladder smooth muscle is mediated solely through the CCK1 receptor subtype, and the antagonist affinity estimates are consistent with those previously obtained in experiments on animal tissue. (C) 2002 Elsevier Science B.V. All rights reserved.