Effects of diadenosine polyphosphates, ATP and angiotensin II on cytosolic Ca2+ activity and contraction of rat mesangial cells.

Diadenosine polyphosphates (Apn A) are known to influence cellular Ca2+ activity ([Ca2+]i) in several cells. Their vasoactive potency has been described in various systems including the kidney. We examined the effects of diadenosine polyphosphates, adenosine 5'-triphosphate (ATP) and angiotensin II (Ang II) on cytosolic Ca2+ activity of mesangial cells (MC) in culture obtained from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. [Ca2+]i was measured as a fluorescence ratio F340/F380 with the fura-2 technique using three excitation wavelengths (340 nm, 360 nm and 380 nm) and a photon counting tube. Resting [Ca2+]i was not significantly different in MC from WKY and SHR rats and was measured as 132 +/- 9 nmol/l (n = 65) and 114 +/- 12 nmol/l (n = 36), respectively. Diadenosine polyphosphates (Ap3A-Ap6A) increased [Ca2+]i transiently with an initial peak and a secondary plateau phase comparable to the effects of ATP or Ang II. Increases in [Ca2+]i induced by all these agonists were not significantly different between MC of WKY and SHR rats. ATP, Ap3A, Ap4A, Ap5A, Ap6A (each 5 micromol/l) increased the fura-2 fluorescence ratio initially by 0.66 +/- 0.09 (n = 33), 0.52 +/- 0.08 (n = 18), 0.25 +/- 0.05 (n = 16), 0.09 +/- 0.06 (n = 7), 0.09 +/- 0.04 (n = 11), respectively. A half-maximal initial increase in the fura-2 fluorescence ratio was reached at 22 nmol/l, 0.9 micromol/l, 2.0 micromol/l and 4.0 micromol/l with Ang II, Ap3A, ATP and Ap4A, respectively. Ap4A (100 micromol/l, n = 18) led to a reversible contraction of MC. Diadenosine polyphosphates increase [Ca2+]i in rat MC, in a similar manner to ATP or Ang II and lead to a contraction of MC, suggesting that these nucleotides are also involved in the control of glomerular haemodynamics.