Premium
Diadenosine polyphosphates induce transplasma membrane calcium influx in cultured glomerular mesangial cells
Author(s) -
TEPEL M.,
HEIDENREICH S.,
SCHLÜTER H.,
BEINLICH A.,
NOFER J.R.,
WALTER M.,
ASSMANN G.,
ZIDEK W.
Publication year - 1996
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1996.400592.x
Subject(s) - ppads , chemistry , adenosine , phospholipase c , phosphatidic acid , extracellular , adenosine triphosphate , medicine , calcium , endocrinology , purinergic receptor , biochemistry , receptor , biology , phospholipid , membrane , organic chemistry
The effects of diadenosine tetraphosphate (AP 4 A) diadenosine pentaphosphate (AP 5 A) and diadenosine hexaphosphate (AP 6 A) on the cytosolic‐free calcium concentration ([Ca 2+ ] i ) were evaluated in cultured rat glomerular mesangial cells (MCs) using the fluorescent dye technique. The addition of 10 μmol L −1 AP 4 A, AP 5 A or AP 6 A significantly increased [Ca 2+ ] i in MCs by 57±9 nmol L −1 n =17; P <0.001), 76±27 nmol L −1 ( n =9; P <0.001) or 65±12 nmol L −1 ( n =18; P <0.01) respectively. In the absence of extracellular calcium, there was no significant change in [Ca 2+ ] i in MCs after administration of diadenosine polyphosphates, indicating that these agents induce transplasma membrane Ca 2+ influx. AP 6 A significantly enhanced the angiotensin II‐induced changes in [Ca 2+ ] i in MCs. The AP 5 A‐induced transplasma membrane Ca 2+ influx was inhibited by the P 2 purinoceptor blockers suramin and pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS), but was not affected by the adenosine A 1 receptor blocker 8‐cyclopentyl‐1.3‐dipropylzanthine (CPDPX). Adenosine triphosphate (ATP) and adenosine 5′‐ O ‐(3‐thio)triphosphate (ATP‐γS) increased [Ca 2+ ] i in MCs, whereas α,β‐methylene ATP had no effect on [Ca 2+ ] i in MCs. Measurements of diacylglycerol and phosphatidic acid showed that AP 5 A and AP 6 A also stimulated phospholipase C, but had no effect on phospholipase D. The inhibition of phosphatidylcholine‐specific phospholipase C significantly reduced the AP 5 A‐induced [Ca 2+ ] i increase. In summary, diadenosine polyphosphates induce Ca 2+ influx through P 2 purinoceptors and may be involved in the local regulation of vascular resistance evoked by the Ca 2+ ‐dependent contractile response of mesangial cells.