The effect of a receptor-mediated Ca2+ entry blocker, 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride (SK&F 96365), on a secretagogue-induced secretory response and Ca2+ dynamics was examined in isolated acini of rat pancreas. SK & F 96365 inhibited the secretory response induced by 100 pM cholecystokinin octapeptide (CCK-8) or 3 microM ethanaminium, 2-[(aminocarbonyl)oxy]-N,N,N-trimethyl,-chloride (carbachol) in isolated incubated acini up to 73.2 +/- 6.1% or 70.3 +/- 3.8% with IC50 of 47.7 microM or 42.0 microM, respectively. The inhibitory effect of SK&F 96365 on the time courses of CCK-8-induced amylase release and [Ca2+]c (cytoplasmic Ca2+ concentration) elevation was further examined in isolated perifused acini or isolated acini loaded with Fura-2. In the 100 pM CCK-8-stimulated preparation, 30 microM SK&F 96365 partly, and 100 microM SK&F 96365 completely, inhibited the sustained plateau phase, but did not inhibit the initial phase of the Ca2+ and secretory responses. In the 5 pM CCK-8-stimulated preparation; (a) 30 microM SK&F 96365 reduced the frequency of the [Ca2+]c oscillations, but caused little, if any, changes in the secretory response; (b) 100 microM SK&F 96365 transformed the oscillatory [Ca2+]c dynamics to a transient increase followed by a gradual decay and caused a significant inhibition of the sustained secretory response. These results indicate that the sustained responses to secretagogues are dependent on a receptor-mediated Ca2+ entry which can selectively be blocked by SK&F 96365 in rat pancreatic acini.