COMPETITIVE-INHIBITION BY PROCAINE OF CARBACHOL-INDUCED STIMULUS-SECRETION COUPLING IN RAT PANCREATIC ACINI

1 Procaine (0.03-10 mM) inhibited carbacbol (CCh)-induced amylase rele ase from rat isolated pancreatic acini in a competitive manner. Kineti c analysis of the relation between CCh concentrations and the amount o f amylase released in the presence of various procaine concentrations indicated that procaine caused competitive inhibition with the affinit y constant (pA2) value of 5.00 +/- 0.08.2 Receptor binding assay confi rmed that procaine (0.01-10 mM) competitively inhibited [N-methyl-H-3] -scopolamine chloride ([H-3]-NMS) binding to its receptor with binding affinity (pK(i)) of 4.63 +/- 0.10. 3 Procaine transformed CCh-evoked [Ca2+]i dynamics: the initial rise in [Ca2+]i followed by a gradual de cay during continuous stimulation with 3 muM CCh was transformed by 0. 3 mM procaine to the oscillatory [Ca2+]i dynamics, which resembled the response to 0.3 muM CCh in the absence of procaine. The initial phase of [Ca2+]i oscillation corresponded to the initial phase of CCh-induc ed amylase release in isolated perfused acini. 4 Procaine (0.3-3 mM) d id not inhibit the secretory response to cholecystokinin octapeptide ( CCK-8) in isolated incubated acini. A higher concentration of procaine (10 mM) caused weak but significant inhibition of the response to onl y limited concentrations of CCK-8, 30 and 100 pM. Procaine lower than 10 mM was ineffective on [I-125]-BH-CCK-8 binding, although procaine ( 10 mM) caused weak but significant inhibition of the binding.