Effects of diadenosine polyphosphates, ATP and angiotensin II on membrane voltage and membrane conductances of rat mesangial cells.
Diadenosine polyphosphates have been shown to influence renal perfusion pressure. As mesangial cells may contribute to these effects we investigated the effects of diadenosine triphosphate (Ap3A), diadenosine tetraphosphate (Ap4A), diadenosine pentaphosphate (Ap5A) and diadenosine hexaphosphate (Ap6A) on membrane voltage (Vm) and membrane conductance (gm) in mesangial cells (MC) of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats in primary and long-term culture. We applied the patch-clamp technique in the fast-whole-cell configuration to measure Vm and gm. To compare the effects of diadenosine polyphosphates with hitherto known agonists we also tested adenosine 5&acute;-triphosphate (ATP) and angiotensin II (Ang II). As there was no significant difference in the Vm values in MC of WKY (-42 +/- 1 mV, n = 70) and SHR rats (-45 +/- 2 mV, n = 99) as well as in the agonist-induced changes of Vm, all data were pooled. The Vm of all the cells was -44 +/- 1 mV (n = 169) and gm was 15.9 +/- 1.8 nS (n = 141). Ion-exchange experiments showed the presence of a K+ and a non-selective cation conductance in resting MC whereas a Cl- conductance or a Na+-selective conductance could not be observed. Ap3A, Ap4A, Ap5A, AP6A and ATP each at a concentration of 5 micromol/l, led to a significant depolarization of Vm by 5 +/- 2 mV (n = 14), 7 +/- 1 mV (n = 25), 3 +/- 1 mV (n = 23), 2 +/- 1 mV (n = 16), and 14 +/- 2 mV (n = 23), respectively. For Ap4A, the most potent diadenosine polyphosphate, we determined the half-maximally effective concentration (EC50) as 6 micromol/l (n = 5-25), for ATP as 2 micromol/l (n = 9-37), and for Ang II as 8 nmol/l (n = 6-18). Ap4A 100 micromol/l increased gm significantly by 55 +/- 20% (n = 16), 100 micromol/l ATP by 135 +/- 60% (n = 18). The diadenosine polyphosphates examined were able to depolarize Vm (Ang II > ATP > Ap4A > Ap3A > Ap5A > Ap6A) by activation of a Cl- conductance and a non-selective cation conductance, as do ATP or Ang II.
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D015226:Dinucleoside Phosphates; D015221:Potassium Channels; D000804:Angiotensin II; C020733:diadenosine tetraphosphate; C011440:diadenosine triphosphate; C070070:diadenosine 5',5''''-P1,P6-hexaphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine