ANTAGONISTIC EFFECT OF CR1409 ON CHOLECYSTOKININ-INDUCED INCREASE IN CYTOSOLIC CALCIUM CONCENTRATION / 中国药理学通报

ABSTRACT

The glutaramic acid derivative cholecystokinin ( CCK ) receptor antagonist, CR1409 was tested for its ability to inhibit CCK induced increase in cytosolic calcium concentration in isolated rat pancreatic acinar cells using fura-2 as calcium probe. Preaddition of 10?mol/L CR1409 completely inhibited the increase of cytosolic calcium concertration induced with 1 nmol/L CCK, but had no antagonistic effect on carbacholine bombesin-induced increase in cytosolic calcium concentration. The half maximal inhibition was obtained for 0.37?mol/L, corresponding to a potency a hundred fold higher than that of db cGMP. In the presence of increasing concentrations of CR1409, the response curves of CCK concentrations were shifted to the right but the same maximum was achieved. Schild representation gave a straight line with a slope close to one ( n = 0.92 ) and pA2 value of 6.93. These findings therefore support that CR1409 is a powerful competitive and specific antagonist bf CCK-induced increase in cytosolic calcium Concentration in isolated rat pancreatic acinar cells and provide further evidence for the role of this ion as an intracellular mediator of pancreatic CCK receptor.