EGF-stimulated aldosterone secretion is mediated by tyrosine phosphorylation but not by phospholipase C in cultured porcine adrenal glomerulosa cells.
We examined the effect of EGF and angiotensin II (AII) on the formation of inositol phosphates and aldosterone secretion, and observed the role of tyrosine phosphorylation in EGF or AII-mediated aldosterone secretion. As cultured glomerulosa cells were incubated with increasing concentrations of EGF (0.01-100 ng/mL), aldosterone secretion increased and reached a plateau at EGF concentration of 10-50 ng/mL. Although EGF alone did increase aldosterone secretion in glomerulosa cells, it did not enhance AII-induced aldosterone secretion when both EGF and AII were added. EGF-induced tyrosine phosphorylation peaked at around 1 min after stimulation and at a concentration of 10-50 ng/mL. AII stimulated tyrosine phosphorylation, but the stimulatory effect was less than that observed in the presence of EGF. Although the latter induced tyrosine phosphorylation of various proteins, it failed to stimulate the formation of inositol phosphates. On the other hand, AII stimulated the production of inositol phosphates in a dose-dependent manner, with maximal stimulation at 10(-8)M. The addition of 10 ng/mL EGF did not affect the AII-induced formation of inositol phosphates. In conclusion, EGF-stimulated aldosterone secretion might be mediated by tyrosine kinase. However, since EGF did not stimulate inositol phospholipid hydrolysis in cultured porcine adrenal glomerulosa cells, its effect does not seem to be mediated by phospholipase C.
Kim
S Y
SY
Department of Internal Medicine, College of Medicine, Seoul National University, Korea. seongyk@plaza.snu.ac.kr
Park
D J
DJ
Lee
H K
HK
D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000096:biosynthesis; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D013552:Swine; D010738:Type C Phospholipases / Q000378:metabolism / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000166:cytology / Q000378:metabolism*
D007295:Inositol Phosphates; D000804:Angiotensin II; D014443:Tyrosine; D000450:Aldosterone; D004815:Epidermal Growth Factor; D010738:Type C Phospholipases