PD 135158, a CCKB/gastrin receptor antagonist, stimulates rat pancreatic enzyme secretion as a CCKA receptor agonist.
The CCKB/gastrin receptor antagonist, PD 135158 (CAM 1028), surprisingly stimulates lipase release from isolated rat pancreatic acini dose dependently in a biphasic manner, with identical efficacy but lower potency compared to cholecystokinin octapeptide (CCK-8). Half-maximal stimulation occurred at 0.6 microM and maximal secretion was induced at 50 microM. Supramaximal concentrations decreased lipase release. Acinar lipase secretion in response to 25 pM CCK-8 or 1 microM CAM-1028 was abolished by 5 microM of the specific CCKA receptor antagonist loxiglumide (CR 1505), half-maximal inhibition was observed at 0.6 microM for CCK-8 and 0.4 microM for PD 135158. These data demonstrate that the CCKB/gastrin receptor antagonist, PD 135158, acts as a full agonist at the rat pancreatic CCKA receptor.
Höcker
M
M
I. Department of Medicine, Christian-Albrechts-University, Kiel, Germany.
Hughes
J
J
Fölsch
U R
UR
Schmidt
W E
WE
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D007211:Indoles / Q000494:pharmacology*; D008049:Lipase / Q000378:metabolism; D008536:Meglumine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D012844:Sincalide / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D007211:Indoles; C065600:PD 135158; D008536:Meglumine; C053737:loxiglumide; D002766:Cholecystokinin; D008049:Lipase; D011377:Proglumide; D012844:Sincalide