Modulation of phospholipase A2 activity and sodium transport by angiotensin-(1-7).
Angiotensin II (Ang II) receptors are coupled to a variety of signal transduction mechanisms. In the kidney, Ang II at nanomolar concentration binds to proximal tubular cells and stimulates phospholipase A2 (PLA2), which in turn catalyzes the hydrolysis of phosphatidylcholine into lysophosphatidylcholine (LPC) and fatty acid. This signal transduction pathway has been shown to be an important modulator of sodium transport. The kidney cortex possesses the enzyme necessary to convert angiotensin I (Ang I) directly to Ang-(1-7) bypassing Ang II as an intermediate. The present investigation was undertaken to determine whether Ang-(1-7) influences epithelial cell function by comparing this heptapeptide with Ang II as a modulator of PLA2 activity and sodium transport. Proximal tubular cells were labeled in tissue culture with 3H-choline and PLA2 activity was measured by quantitation of LPC. We found that Ang II (10(-9) M to 10(-6) M) significantly increased PLA2 activity (154 +/- 36% to 209 +/- 94%). Similar results were obtained with Ang-(1-7) (240 +/- 130% to 353 +/- 40%). The bioactivity of the peptides was assayed by its ability to regulate transcellular 22Na flux. Ang II (10(-9) M) inhibited 22Na flux by 12 +/- 2% while Ang-(1-7) (10(-9) M) inhibited 22Na flux by 20 +/- 5%. These results suggest that one potential role of Ang-(1-7) in the regulation of kidney epithelial electrolyte transport may involve activation of PLA2.
Andreatta-van Leyen
S
S
Department of Physiology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Romero
M F
MF
Khosla
M C
MC
Douglas
J G
JG
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*
D008244:Lysophosphatidylcholines; D010446:Peptide Fragments; D000804:Angiotensin II; C014805:angiotensin II, Sar(1)-Thr(8)-; C040776:5,6-epoxy-8,11,14-eicosatrienoic acid; D000803:Angiotensin I; D012964:Sodium; D010741:Phospholipases A; D054467:Phospholipases A2; D015126:8,11,14-Eicosatrienoic Acid; C118790:angiotensin I (1-7)