title: Alpha 1-adrenoceptor subtypes mediating stimulation of Na+,K(+)-ATPase activity in rat renal proximal tubules.
abstract: Although both alpha 1A- and alpha 1B-adrenoceptors are present in renal proximal tubules, the involvement of these receptor subtypes in the stimulation of Na+,K(+)-ATPase activity is not known. This study was undertaken to delineate the receptor subtype(s) involved in alpha 1-adrenoceptor-mediated increase in Na+,K(+)-ATPase activity and to identify the cellular signaling mechanisms such as stimulation of inositol triphosphate formation (IP3) and protein kinase C activation in this phenomenon. It was found that norepinephrine-induced increase in Na+,K(+)-ATPase activity was attenuated by prazosin, but not by rauwolscine, indicating the involvement of alpha 1-adrenoceptors. Furthermore, this response was selectively inhibited by the alpha 1B-adrenoceptor inactivator, chloroethylclonidine (100 microM), but not by the alpha 1A-adrenoceptor antagonist, WB4101 (0.01 microM). We examined whether these effects on Na+,K(+)-ATPase activity are mediated via the activation of IP3 and protein kinase C. Phenylephrine-induced increase in IP3 levels was abolished by prazosin, and significantly inhibited by WB4101, but not by chloroethylclonidine. Similarly, phenylephrine-induced activation of protein kinase C was sensitive to blockade by WB4101, but not by chloroethylclonidine. These results suggest that whereas both alpha 1A- 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.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences College of Pharmacy, University of Houston, TX 77024-5515, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Gopalakrishnan
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: M F
authors.initials: MF
authors.lastname: Lokhandwala
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013268:Stimulation, Chemical
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D009638:Norepinephrine