title: Role of PKC and calcium in modulation of effects of angiotensin II on sodium transport in proximal tubule.
abstract: It has been well documented that low concentrations of ANG II (10(-11) to 10(-10) M) stimulate, whereas high concentrations of ANG II (10(-8) to 10(-5) M) inhibit Na(+) transport in proximal tubules of rat and rabbit kidneys. Measured ANG II concentration in proximal tubular fluid is in the nanomolar range. In the present study, we investigated the role of PKC, intracellular Ca(2+), and cAMP in modulating the effects of luminal ANG II on Na(+) absorption by microperfusion techniques in rabbit superficial segment of proximal tubules in vitro. We confirmed that ANG II (10(-9) M) had no change on fluid absorption (J(v)); however, fluid absorption increased significantly when 10(-9) M ANG II and 3,4,5-trimethoxybenzoic acid-8-(diethylamino)octyl ester (TMB-8), a blocker of intracellular calcium mobilization, were added together. In contrast, ANG II significantly decreased J(v) when PKC was inhibited. When 10(-9) M ANG II was present together with 1-(5-isoquinolinesulfonyl)-2-mehtylpiperazine and TMB-8, no significant change of J(v) occurred. Inhibition of endogenous cAMP activity by a PKA inhibitor did not change either basal or ANG II-stimulated fluid absorption. Our results indicate that ANG II regulates Na(+) absorption by a cAMP-independent mechanism and that PKC and intracellular calcium both play a critical role in modulating the effects of physiological concentration of ANG II on proximal tubule transport. Balance between these two cytosolic messengers modulates the effects of ANG II on fluid absorption in the proximal tubule.
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8026, USA.
authors.forename: Zhaopeng
authors.initials: Z
authors.lastname: Du
authors.forename: William
authors.initials: W
authors.lastname: Ferguson
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D014867:Water / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D014867:Water; D000804:Angiotensin II; D012964:Sodium; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002118:Calcium