Receptor type for cholecystokinin on isolated intestinal muscle cells of the guinea pig.
Smooth muscle cells isolated from the longitudinal muscle layer of guinea pig ileum were used to determine the presence and type of cholecystokinin/gastrin receptor mediating contraction. This was accomplished with a series of cholecystokinin and gastrin agonists (CCK-8, des(SO3)CCK-8, gastrin-17, des(SO3)gastrin-17 and pentagastrin) and antagonists (glutaramic acid derivatives CR 1392, CR 1409, CR 1505 and proglumide). The order of potency of agonists based on EC50 values derived from concentration-response curves was: CCK-8 greater than des(SO3)CCK-8 greater than gastrin-17 greater than des(SO3)gastrin-17. The inhibitory dissociation constant (Ki) for the antagonist CR 1505 derived from Schild plots was the same whether sulfated CCK-8 or desulfated gastrin-17 was used as agonist (4.47 +/- 0.76 versus 4.68 +/- 0.78 nM). Pentagastrin acted as a partial agonist and inhibited partially the response to CCK-8. The Ki values determined for all antagonists with pentagastrin as agonist were similar to those with CCK-8 as agonist. The order of potency of agonists and the independence of Ki values from the type of agonist used implied that CCK and gastrin interact with one receptor type; the receptor is more sensitive to CCK-8 but is minimally influenced by sulfation of the tyrosine residue. In this respect, the receptor appears to be distinct from the CCK receptor on gallbladder muscle cells and pancreatic acinar cells.
Morini
G
G
Institute of Pharmacology and Pharmacognosy, University of Parma, Italy.
Barocelli
E
E
Impicciatore
M
M
Grider
J R
JR
Makhlouf
G M
GM
D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000008:administration & dosage / Q000494:pharmacology; D006168:Guinea Pigs; D006728:Hormones / Q000008:administration & dosage / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010418:Pentagastrin / Q000008:administration & dosage / Q000494:pharmacology; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism*
D005755:Gastrins; D006728:Hormones; D011949:Receptors, Cholecystokinin; C013550:gastrin 17; C053737:loxiglumide; D002766:Cholecystokinin; D010418:Pentagastrin; D011377:Proglumide