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 (ApsA) and diadenosine hexaphosphate (Ap6A) on membrane voltage (Vm) and membrane conductance (gin) 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-wholecell configuration to measure Vm and gin. TO compare the effects of diadenosine polyphosphates with hitherto known agonists we also tested adenosine 5"-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 V~ of all the cells was -44+lmV (n=169) and gm was 15.9+1.8nS (n = 141). Ion-exchange experiments showed the presence of a K + and a non-selective cation conductance in resting MC whereas a C1-conductance or a Na +selective conductance could not be observed. Ap3A, Ap4A, ApsA, AP6A and ATP each at a concentration of 5 gmol/1, led to a significant depolarization of Vm by 5+2mV (n=14), 7+lmV (n=25), 3+lmV (n=23), 2+lmV(n=16), and 14+2mV(n=23), respectively. For Ap4A, the most potent diadenosine polyphosphate, we determined the half-maximally effective concentration (ECso) as 6 gmol/1 (n = 5-25), for ATP as 2 gmol/1 (n = 9-37), and for Ang II as 8 nmol/1 (n = 6-18). Ap4A 100 gmol/1 increased gm significantly by 55 + 20% (n = 16), 100 pmol/1ATP