ALTERATIONS OF THE PANCREATIC SECRETORY RESPONSES TO SECRETIN AND TO THE IONOPHORE A23187 BY RESERPINE - A CALCIUM-MEDIATED PHENOMENON

This study was undertaken to further characterize the secretory respon se of the rat pancreas after reserpine treatment. Rats were given rese rpine (1 mg kg(-1) day(-1) i.p.) or vehicle for 7 days. To distinguish between specific effects of reserpine and those related to secondary malnutrition caused by the drug, the secretory response of a group of pair-fed (PF) animals to reserpine was also investigated. Amylase rele ase from dispersed pancreatic acini, prepared from control (C), PF and reserpine-treated (R) rats were used to evaluate functional secretory capacity. Reserpine and pair-feeding caused reduced responses of panc reatic acini to secretin. The pair-feeding-altered secretin response w as greatly improved by increasing extracellular Ca2+ concentration, wh ereas a slight improvement was noticed in the R group. Reserpine signi ficantly reduced the secretory response to the ionophore A23187 at con centrations above 5 x 10(-7) M in 1.25 mM Ca2+; in 2.5 mM Ca2+, the re sponse to the ionophore was significantly higher in the R group than i n C at all ionophore concentrations. Furthermore, at 2 x 10(-7) M iono phore, the secretory response to secretin in the R group became signif icantly higher than that in the C group but comparable to that of the control + ionophore. In conclusion, reserpine affects the secretory re sponse to secretin as did pre-exposure of pancreatic acini to a high c oncentration of carbamylcholine. The modified secretory response to th e ionophore following reserpine treatment indicates that reserpine may act as a 'Ca2+ entry mechanism' antagonist which may explain the part ial reduction in the secretin response.