title: Pharmacological characterization of cholecystokinin receptors mediating contraction of human gallbladder and ascending colon.
abstract: 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 CCK(1) and CCK(2) 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 CCK(1) 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 +/- .33). In both tissues, the CCK(2) 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 CCK(1) receptor subtype, and the antagonist affinity estimates are consistent with those previously obtained in experiments on animal tissue.
authors.affiliation: Academic Department of Surgery, Rayne Institute, GKT Schools of Medicine and Dentistry, London SE5 9NU, UK. mmorton1@prius.jnj.com
authors.forename: M F
authors.initials: MF
authors.lastname: Morton
authors.forename: N J
authors.initials: NJ
authors.lastname: Welsh
authors.forename: I A
authors.initials: IA
authors.lastname: Tavares
authors.forename: N P
authors.initials: NP
authors.lastname: Shankley
mesh_terms: D002766:Cholecystokinin / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005704:Gallbladder / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects*; D009924:Organ Culture Techniques; D010418:Pentagastrin / Q000494:pharmacology; D010528:Peristalsis / Q000187:drug effects; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C090019:8-sulfocholecystokinin octapeptide; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D010418:Pentagastrin; D012844:Sincalide