REGULATION OF CAMP PRODUCTION IN INITIAL AND TERMINAL INNER MEDULLARYCOLLECTING DUCTS

Background. The inner medullary collecting duct (IMCD) is composed of at least two functionally and morphologically distinct segments, the i nitial (IMCDi) and the terminal (IMCDt) portions. However, most studie s of receptor signaling have been performed on cells obtained from the entire inner medulla. The purpose of this study was to determine whet her the patterns oi receptor-activated cAMP accumulation were differen t between these segments. Methods. We measured cAMP accumulation stimu lated by vasopressin and isoproterenol, and the effect of epinephrine in freshly dissected IMCDi and IMCDt segments cultured and IMCDi and I MCDt cells in primary culture. Results. The maximum response to vasopr essin was twofold higher in fresh IMCDt versus IMCDi (P < 0.05), howev er, it increased in cultured IMCDi by 40% versus fresh cells with no c hange in the response in fresh versus cultured IMCDt. The maximum resp onse to isoproterenol was small in fresh cells but increased by five- and sixfold, respectively, in cultured IMCDi and IMCDt cells. alpha(2) -Adrenoceptor stimulation almost completely inhibited both vasopressin and isoproterenol-stimulated cAMP accumulations in fresh IMCDi and IM CDt cells, but only partially inhibited either accumulation by 34 to 4 9% in cultured cells. Conclusions. (1) IMCDi and IMCDt cells are both subject to vasopressin and alpha(2)- and beta-adrenergic regulation of adenylyl cyclase activity; (2) the relative influence of beta-adrener gic, alpha(2)-adrenergic and V-2 receptors to affect cAMP accumulation is altered in primary culture versus freshly dissected IMCD segments, suggesting that caution must be exercised in the extrapolation of dat a from cultured IMCD cells to bl vivo models.