Modulation by verapamil of hormonal action on the Henle's loop of mice

Abstract

In order to know the role of cytosolic calcium in the modulation of the hormone action on sodium chloride transport across the thick ascending limbs of Henle's loop, we examined whether verapamil, a blocker of cellular calcium entry, can modulate the effects of arginine vasopressin (AVP) or glucagon in stimulating transepithelial voltage (Vt) and cyclic AMP generation in the mouse medullary thick ascending limb (MAL). The pretreatment of the renal tubule with 5 X 10(-5)M verapamil reduced the Vt stimulated with 200 microU/mliter AVP from 1.7 +/- 0.3 mV to 0.4 +/- 0.4 mV (N = 7, P less than 0.05). The changes in Vt were well correlated with those of unidirectional Cl flux from the lumen to the bath. However, verapamil did not influence the Vt stimulated with 10(-3) M dibutyryl cyclic AMP. The pretreatment of the MAL with 10(-5) M verapamil also inhibited the cyclic AMP generation in the MAL from 72.1 +/- 17.9 to 50.6 +/- 13.6 fmoles/mm/7 min (N = 7, P less than 0.05) as well as in the medullary collecting tubule from 147.6 +/- 46.6 to 121.2 +/- 41.6 fmoles/mm/7 min (N = 4, P less than 0.05). The effect of verapamil in inhibiting the AVP-stimulated cAMP was dose-dependent: the cAMP generation was inhibited by 28.9 +/- 6.8 and 61.1 +/- 9.3% with 10(-5) M and 10(-4) M verapamil, respectively. When verapamil was added to the medium simultaneously with AVP, the generation of cyclic AMP was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)