title: Full and partial relaxing CCK-C-terminal fragments in hog duodenal circular muscle.
abstract: The essential active moieties in the cholecystokinin (CCK) ligand for relaxing duodenal circular muscles of pigs were investigated. The decrease in isotonic tension from the normal tone was expressed as a percentage of the relaxation obtained with Ca2+-free EGTA (2 mM) solution. Inhibition was expressed as a percentage of the relaxation induced by CCK-C-terminal tetrapeptide (CCK-4, 4.23 microM) without antagonists. Amino acid sequences from CCK-(27-28) to CCK-(27-31) increased the potency. CCK-(27-30) or CCK-(27-31) attained the same extent of relative intrinsic activity as CCK-8. The amino acid sequence from Tyr27, CCK-(27), to Trp30, CCK-(30), is another prerequisite for relaxation, in addition to the sequence of CCK-4. Newly synthesized CCK-(27-30)-R derivatives with increasingly bulky substituents (R = H, ethyl, phenyl, n-butyl and allyl) were changed from full agonists to partial agonists. Phenyl, n-butyl and allyl derivatives of CCK-(27-30)-R, in particular, had a mixed agonist and antagonist action. CCK-(27-30)-allyl antagonized competitively the CCK-4-induced relaxation (IC50 = 123 (75.9-200) microM).
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004386:Duodenum / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D002766:Cholecystokinin