Alterations of the Pancreatic Secretory Responses to Secretin and to the lonophore A23187 by Reserpine: A Calcium-Mediated Phenomenon?

Abstract

This study was undertaken to further characterize the secretory response of the rat pancreas after reserpine treatment. Rats were given reserpine (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 release 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 pancreatic acini to secretin. The pair-feeding-altered secretin response was greatly improved by increasing extracellular Ca²⁺ concentration, whereas a slight improvement was noticed in the R group. Reserpine significantly reduced the secretory response to the ionophore A23187 at concentrations above 5 × 10^-7M in 1.25 mM Ca²⁺; in 2.5 mM Ca²⁺, the response to the ionophore was significantly higher in the R group than in C at all ionophore concentrations. Furthermore, at 2 × 10^-7M ionophore, the secretory response to secretin in the R group became significantly higher than that in the C group but comparable to that of the control + ionophore. In conclusion, reserpine affects the secretory response to secretin as did pre-exposure of pancreatic acini to a high concentration of carbamylcholine. The modified secretory response to the ionophore following reserpine treatment indicates that reserpine may act as a ‘Ca²⁺ entry mechanism’ antagonist which may explain the partial reduction in the secretin response.