ALPHA(1)-ADRENOCEPTOR SUBTYPES MEDIATING STIMULATION OF NA-ATPASE ACTIVITY IN RAT RENAL PROXIMAL TUBULES(,K+)

Although both alpha(1A)- and alpha(1B)-adrenoceptors are present in re nal proximal tubules, the involvement of these receptor subtypes in th e stimulation of Na+,K+-ATPase activity is not known. This study was u ndertaken to delineate the receptor subtype(s) involved in alpha(1)-ad renoceptor-mediated increase in Na+,K+-ATPase activity and to identify the cellular signaling mechanisms such as stimulation of inositol tri phosphate formation (IP3) and protein kinase C activation in this phen omenon. It was found that norepinephrine-induced increase in Na+,K+-AT Pase activity was attenuated by prazosin, but not by rauwolscine, indi cating the involvement of alpha(1)-adrenoceptors. Furthermore, this re sponse was selectively inhibited by the alpha(1B)-adrenoceptor inactiv ator, chloroethylclonidine (100 mu M), but not by the alpha(1A)-adreno ceptor antagonist, WB4101 (0.01 mu M). We examined whether these effec ts on Na+,K+-ATPase activity are mediated via the activation of IP3 an d protein kinase C. Phenylephrine-induced increase in IP3 levels was a bolished by prazosin, and significantly inhibited by WB4101, but not b y chloroethylclonidine. Similarly, phenylephrine-induced activation of protein kinase C was sensitive to blockade by WB4101, but not by chlo roethylclonidine. These results suggest that whereas both fake alpha(1 A)- and alpha(1B)-adrenoceptors are present in proximal tubules, alpha (1B)-adrenoceptors are involved in stimulating Na+,K+-ATPase activity and alpha(1A)-adrenoceptors are predominantly linked to renal tubular IP3 production and protein kinase C activation. Therefore, it appears that norepinephrine-induced stimulation of Na+,K+-ATPase activity does not involve phospholipase-C-coupled protein kinase C pathway.