Characterization of CCK receptor-mediated effects on intracellular calcium of porcine chief cells.
Effects of cholecystokinin (CCK) receptor agonists and antagonists on intracellular calcium ¿[Ca2+]i¿ of isolated porcine chief cells were determined by FURA2 fluorometry. CCK-8 increased [Ca2+]i with an EC50 of 6 nmol/l. The CCKB receptor preferring agonists gastrin-17-I, desulfated CCK-8 and CCK-4 had only small stimulatory effects (< 12% of maximal CCK-8 effect, EC50's in the low nanomolar range) and did not inhibit the CCK-8 response, suggesting that they were acting at CCKB but not, as partial agonists, at CCKA receptors. A71378 had its main stimulatory effect in low and a slight additional effect in high concentrations (EC50 80 pmol/l and > 1 mumol/l), respectively, while A72962 had its main stimulatory effect in high concentrations (EC50 > 1 mumol/l). The CCK receptor antagonists L364.718, L365.260, CBZ-CCK27-32 and dibutyryl cGMP inhibited CCK-8 (100 nmol/l) response concentration-dependently with IC50's of 540 pmol/l, 2mumol/l, 3 mumol/l and 250 mumol/l, respectively. These results suggest that CCK effects on [Ca2+]i of porcine chief cells are mainly (> 80%) mediated via CCKA receptors, which differ from guinea-pig and rabbit chief cell receptors by a higher distinction capacity between selective CCKA and CCKB, receptor agonists (A71378 versus A72962) and antagonists (L364.718 versus L365.260) and by the apparent lack of activation by desulfated CCK-8 and gastrin-17-I. Isolated porcine chief cells therefore appear to be a favourable "in vitro" system to characterize CCKA receptor specific compounds.
Heim
H K
HK
Institute of General Pharmacology, Medical School Hannover, FRG.
Elhöft
A
A
Wittstock
H
H
Sewing
K F
KF
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016257:Fura-2; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D011949:Receptors, Cholecystokinin / Q000819:agonists* / Q000037:antagonists & inhibitors*; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013552:Swine
D011949:Receptors, Cholecystokinin; D012844:Sincalide; D002118:Calcium; D016257:Fura-2