Epidermal growth factor is a potent inhibitor of renin secretion.
Epidermal growth factor (EGF) is not only a cell mitogen but a potent vasoconstrictor that shares many properties with angiotensin II. Because EGF is localized in the kidney, we have studied the direct effects of EGF on renin secretion using both static incubations and perifusions of rat renal cortical slices. EGF at 5 x 10(-9) M significantly inhibited renin secretion in static incubations (control, 100 +/- 3%; EGF, 72 +/- 3%; p < 0.001). When added to perifusions, EGF acted rapidly, reducing renin secretion at the earliest time period (10 minutes). Similarly, transforming growth factor-alpha, which can bind to the EGF receptor, also inhibited renin secretion (control, 92 +/- 8%; transforming growth factor-alpha [2 x 10(-9) M], 63 +/- 4%; p < 0.02). Because both prostaglandins and lipoxygenase products of arachidonic acid have been shown to play a role in some EGF-mediated actions, we examined these possible mechanisms of EGF action. Meclofenamate, a cyclooxygenase blocker, and BW755c and baicalein, both lipoxygenase blockers, were studied. None of these agents altered EGF-mediated renin inhibition. EGF action has also been coupled to the stimulation of tyrosine kinase activity; therefore, we examined the effects of the tyrosine kinase inhibitors genistein and quercetin. Both genistein (10(-5) M) and quercetin (10(-5) M) abolished the inhibition of renin by EGF (control, 100 +/- 3%; EGF, 82 +/- 4%; EGF plus genistein, 110 +/- 7%; p < 0.01; EGF, 75 +/- 4%; EGF plus quercetin, 92 +/- 4%; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
USC Medical Center, Division of Endocrinology, Los Angeles 90033.
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D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000092502:Renin Inhibitors
D000804:Angiotensin II; D016861:Cyclooxygenase Inhibitors; D004815:Epidermal Growth Factor; D019833:Genistein; D007529:Isoflavones; D011505:Protein-Tyrosine Kinases; D012083:Renin; D013755:Tetradecanoylphorbol Acetate; D000092502:Renin Inhibitors