EXTRACELLULAR UREA CONCENTRATION MODULATES CAMP PRODUCTION IN THE MOUSE MTAL

Ionic reabsorption along the ascending limb of Henle's loop (TAL) is c ontrolled by hormonal stimulation. Most of the hormones that affect th is reabsorption regulate ionic transporter activity via cAMP, and some of these hormonal actions have been shown to be modulated by intersti tial osmolarity. We studied the early effects of increasing extracellu lar urea concentration on the production of cAMP induced by arginine v asopressin (AVP) and forskolin in a suspension of medullary portions o f TAL (MTAL) prepared from mouse kidney. The addition of urea, perform ed fifteen minutes before adenylyl cyclase stimulation, decreased both AVP- and forskolin-induced cAMP production. This effect. observed bot h in the presence and the absence of phosphodiesterase inhibition, was optimal with 300 mmol/liter urea. Addition of urea to the extracellul ar medium disturbed several cellular parameters, but the decrease in c AMP production appeared to be mediated by the activation of both the p rotein kinase A and a phosphatase rather than by the modifications in phospholipid metabolism. Since cAMP is the major cytosolic transductio nal factor in MTAL cells, urea present in the medullary interstitium m ay thus be considered as an important modulator of hormonal actions in this segment of the nephron.