The effect of calcium channel blockade on basal- and substance P-induced intestinal secretion

Calcium plays a central role in modulating many physiologic events. We have investigated the role of calcium channel blockade in the control of basal (n = 6)- and substance P-stimulated (n = 6) intestinal transport in the isolated perfused rabbit ileum. Twenty-centimeter segments of ileum, harvested from New Zealand rabbits, were arterially perfused at 1.5 ml/min with an oxygenated modified Krebs buffer solution containing washed human red cells (Hct = 15-20%) and 2.5 mM Ca2+. The intestinal lumen was perfused at 2 ml/min with an isotonic solution containing 1.2 mM Ca2+ and [14C]PEG as a nonabsorbable volume marker. The infusion of verapamil (1 microgram/min) significantly reduced (P less than 0.05) the basal secretion of H2O, and Cl-. Verapamil prevented the secretory effect of substance P infused at 0.25 microgram/min. Intraarterial verapamil had no effect on vascular perfusion pressure. These data indicate that calcium channel blockade has significant effects on basal- and substance P-stimulated intestinal secretion and suggest that transmembrane calcium fluxes function as major determinants of basal- and secretagogue-stimulated intestinal transport.