Adenosine stimulates Ca2+ fluxes and increases cytosolic free Ca2+ in cultured rat mesangial cells.
Adenosine has been associated with cellular Ca2+ metabolism in some cell types. Since adenosine is able to contract glomerular mesangial cells in culture, and since Ca2+ is the main messenger mediating contractile responses, we studied the effect of adenosine on 45Ca2+ movements into and out of mesangial cells and on the cytosolic free Ca2+ concentration ([Ca2+]i). Adenosine at 0.1 mM increased 45Ca2+ uptake (basal, 9993 +/- 216; + adenosine, 14823 +/- 410 d.p.m./mg; P less than 0.01) through verapamil-sensitive Ca2+ channels. These channels seem to be of the A1-adenosine receptor subtype. Adenosine also stimulated 45Ca2+ efflux from 45Ca(2+)-loaded mesangial cells. This effect was accompanied by a net depletion of intracellular 45Ca2+ content under isotopic equilibrium conditions (basal, 24213 +/- 978; + adenosine, 18622 +/- 885 d.p.m./mg; P less than 0.05). The increase in 45Ca2+ efflux was inhibited by a Ca(2+)-free medium or in the presence of 10 microM-verapamil. However, the intracellular Ca(2+)-release blocker TMB-8 (10 microM) only partially inhibited the adenosine-stimulated 45Ca2+ efflux. In addition, adenosine induced an elevation in [Ca2+]i in mesangial cells with an initial transient peak within 15 s (basal, 113 +/- 7; adenosine, 345 +/- 46 nM), and a secondary increase which was slower (3-4 min) and of lower magnitude than the initial peak (250 +/- 21 nM). In summary, adenosine elevates [Ca2+]i and stimulates both Ca2+ uptake from the extracellular pool and Ca2+ efflux from intracellular pools in mesangial cells. The Ca2+ release from internal stores is produced by a combination of a TMB-8-inhibitable and a non-TMB-8-inhibitable mechanism, and seems to be dependent on Ca2+ influx.
Olivera
A
A
Medical Research Institute, Fundación Jiménez Díaz/Consejo Superior de Investigaciones Científicas, Madrid, Spain.
López-Rivas
A
A
López-Novoa
J M
JM
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D002132:Calcium Radioisotopes; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D016257:Fura-2; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical
D002132:Calcium Radioisotopes; D011189:Potassium Chloride; D000241:Adenosine; D002118:Calcium; D016257:Fura-2