Verapamil and quinidine effects on PAH transport by isolated perfused renal tubules.

Abstract

The effects of verapamil and quinidine on p-aminohippurate (PAH) transport by isolated perfused snake (Thamnophis spp.) distal-proximal renal tubules were studied. Addition of 5 X 10(-5) M verapamil or 1 X 10(-4) M quinidine to the bath reversibly depressed net PAH secretion (JnetPAH), apparent permeabilities of luminal (PL) and peritubular membranes (Pp) to PAH, and initial rate of PAH transport into cells at the peritubular membrane without affecting net fluid absorption (Jv), but simultaneously produced a threefold increase in cellular PAH concentration ( [PAH]cell). Addition of 5 X 10(-5) M verapamil to the perfusate reversibly depressed JnetPAH and PL without affecting [PAH]cell or Jv. Tetraethylammonium (1 X 10(-3) M) did not alter the effects of verapamil on PAH transport. The data indicate that verapamil and quinidine in the bath inhibit JnetPAH by inhibiting uptake into cells across peritubular membrane and efflux from cells across luminal and peritubular membranes and possibly by producing intracellular binding, verapamil in the perfusate inhibits JnetPAH by inhibiting efflux from cells across the luminal membrane and probably uptake into cells across the peritubular membrane, and the verapamil effects on JnetPAH do not depend on its entry into cells. The effects of verapamil may result primarily from inhibition of calcium entry into cells, but both verapamil and quinidine may have effects on PAH transport independent of effects on calcium.