Mercury chloride as a possible phospholipase C activator: effect on angiotensin II-induced [Ca++]i transient in the rat early proximal tubule.
In our previous report (Biochem. Biophys. Res. Commun. 165(3), 1221-1228, 1989), we have demonstrated the biphasic increase of intracellular free calcium concentration ([Ca++]i) induced by angiotensin II (ANG II) in isolated rat early proximal tubule (S1). The present study was undertaken to determine the effect of HgCl2 on ANG II-induced [Ca++]i increase using Fura-2. HgCl2 (10(-10) M2-10(-8) M) potentiated the [Ca++]i increase induced by ANG II (10(-11) M) in a dose-dependent manner. To determine the mechanism of stimulatory effect by HgCl2 on ANG II-induced [Ca++]i increase, nephron segments were pretreated with 10(-4) M propranolol, a phospholipase C inhibitor. The stimulatory effect by 10(-9) M HgCl2 in 10(-11) M ANG II-induced [Ca++]i increase was completely inhibited by propranolol. Moreover, 10(-4) M propranolol completely blocked the stimulatory effect of HgCl2 on ANG II-mediated IP3 production. This study suggests for the first time that HgCl2 stimulates the [Ca++]i increment induced by ANG II, possibly through an activation of phospholipase C.
Jung
K Y
KY
Department of Pharmacology, Faculty of Medicine, University of Tokyo, Japan.
Endou
H
H
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D016257:Fura-2 / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008628:Mercury / Q000008:administration & dosage / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D010738:Type C Phospholipases / Q000378:metabolism*
D000804:Angiotensin II; D015544:Inositol 1,4,5-Trisphosphate; D011433:Propranolol; D010738:Type C Phospholipases; D008628:Mercury; D002118:Calcium; D016257:Fura-2