title: Cholecystokinin-B receptor ligands of the dipeptoid series act as agonists on rat stomach histidine decarboxylase.
abstract: OBJECTIVE
  The effect of gastrin on the enterochromaffin-like cells in the rat stomach is mediated by cholecystokinin (CCK)-B receptors and manifested as activation of histidine decarboxylase (HDC). The dipeptoids PD 136450, PD 135158, and PD 134308 are thought to be selective CCK-B receptor antagonists. The effects of the dipeptoids and of gastrin-17 and sulfated CCK-8 on rat stomach HDC activity were examined.
  
  
  METHODS
  Drugs were infused intravenously or subcutaneously to fasted rats, and the HDC activity was determined.
  
  
  RESULTS
  The dipeptoids activated HDC with maximal responses (50%-60% of the maximal response to gastrin) at 1 mumol.kg-1.h-1. Rat gastrin-17 activated HDC maximally at 3 nmol.kg-1.h-1, and sulfated CCK-8 produced maximal response at 20 nmol.kg-1.h-1. The CCK-B receptor antagonist L-365,260 inhibited the HDC activation induced by gastrin, sulfated CCK-8, or the dipeptoids. The dipeptoids did not inhibit the gastrin-induced HDC activation.
  
  
  CONCLUSIONS
  Gastrin, sulfated CCK-8, and the dipeptoids activated rat stomach HDC. L-365,260 but not devazepide inhibited the HDC activation. Thus, the dipeptoids, which failed to inhibit the gastrin-induced HDC activation, act as CCK-B receptor agonists and not as antagonists. It is important to recognize this to ensure appropriate interpretation of data obtained with these drugs.
authors.affiliation: Department of Pharmacology, University of Lund, Sweden.
authors.forename: X Q
authors.initials: XQ
authors.lastname: Ding
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Håkanson
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D020109:Devazepide; D004789:Enzyme Activation; D005755:Gastrins / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology*; D010671:Phenylurea Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology; D013270:Stomach / Q000201:enzymology*
chemical_list: D001570:Benzodiazepinones; D005755:Gastrins; D007211:Indoles; D008024:Ligands; D010627:Phenethylamines; D010671:Phenylurea Compounds; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C065600:PD 135158; C065599:PD 134308; C077645:PD 136450; C058121:L 365260; C013550:gastrin 17; D008536:Meglumine; D006640:Histidine Decarboxylase; D020109:Devazepide; D012844:Sincalide