Diadenosine polyphosphates induce transplasma membrane calcium influx in cultured glomerular mesangial cells.
The effects of diadenosine tetraphosphate (AP4A) diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A) on the cytosolic-free calcium concentration ([Ca2+]i) were evaluated in cultured rat glomerular mesangial cells (MCs) using the fluorescent dye technique. The addition of 10 mumol L-1 AP4A, AP5A or AP6A significantly increased [Ca2+]i in MCs by 57 +/- 9 nmol L-1 n = 17; P < 0.01), 76 +/- 27 nmol L-1 (n = 9; P < 0.01) or 65 +/- 12 nmol L-1 (n = 18; P < 0.01) respectively. In the absence of extracellular calcium, there was no significant change in [Ca2+]i in MCs after administration of diadenosine polyphosphates, indicating that these agents induce transplasma membrane Ca2+ influx. AP6A significantly enhanced the angiotensin II-induced changes in [Ca2+]i in MCs. The AP5A-induced transplasma membrane Ca2+ influx was inhibited by the P2 purinoceptor blockers suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), but was not affected by the adenosine A1 receptor blocker 8-cyclopentyl-1.3-dipro-pylzanthine (CPDPX). Adenosine triphosphate (ATP) and adenosine 5'-O-(3-thio)triphosphate (ATP-gamma S) increased [Ca2+]i in MCs, whereas alpha, beta-methylene ATP had no effect on [Ca2+]i in MCs. Measurements of diacylglycerol and phosphatidic acid showed that AP5A and AP6A also stimulated phospholipase C, but had no effect on phospholipase D. The inhibition of phosphatidylcholine-specific phospholipase C significantly reduced the AP5A-induced [Ca2+]i increase. In summary, diadenosine polyphosphates induce Ca2+ influx through P2 purinoceptors and may be involved in the local regulation of vascular resistance evoked by the Ca(2+)-dependent contractile response of mesangial cells.
Tepel
M
M
Marienhospital Herne, Ruhr-Universität-Bochum, Germany.
Heidenreich
S
S
Schlüter
H
H
Beinlich
A
A
Nofer
J R
JR
Walter
M
M
Assmann
G
G
Zidek
W
W
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000345:Affinity Labels / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010739:Phospholipase D / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D015290:Second Messenger Systems; D013498:Suramin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000345:Affinity Labels; D015226:Dinucleoside Phosphates; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C022571:adenosine 5'-O-(3-thiotriphosphate); C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; C020733:diadenosine tetraphosphate; C070070:diadenosine 5',5''''-P1,P6-hexaphosphate; D013498:Suramin; D000255:Adenosine Triphosphate; D010738:Type C Phospholipases; D010739:Phospholipase D; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium