Calcitonin is a competitive inhibitor of the hydrosmotic effect of oxytocin in toad bladder

Abstract

The effects of calcitonin (CT) on the water transfer in the toad (Bufo arenarum) urinary bladder, an epithelial barrier commonly employed as a model of the mammalian nephron, were studied. The net transmembrane water flux was measured at minute intervals, while the endogenous adenosine 3',5'-cyclic monophosphate (cAMP) levels were determined in isolated epithelial cells. It was observed that 1) CT, up to 10(-6) M, did not have any effect on water permeability. 2) Preincubation with CT, between 10(-7) and 10(-8) M, inhibited the hydrosmotic response to a supramaximal dose of oxytocin (OXT; 2 x 10(-8) M), used here as an antidiuretic hormone (ADH) analogue. This inhibition was reversible and concentration related. Nevertheless, although the magnitude of the response was reduced, its time course of evolution did not change. 3) When CT was added on the previously developed response to OXT, inhibition was also dose dependent with a time course not distinguishable from hormonal washout. 4) CT, up to 10(-6) M, did not modify the hydrosmotic response to 8-bromo cAMP, a potent analogue of the ADH second messenger. 5) CT and OXT increased the intracellular cAMP levels, but both effects were not cumulative. The increase induced by CT plus OXT was significantly lower than the one elicited by OXT alone. It is concluded that CT is a competitive inhibitor to the hydrosmotic effect of OXT in toad urinary bladder. Its action must be located prior to cAMP formation.