Effect of atrial natriuretic peptide and calcium antagonists on platelet-activating factor-induced contraction and intracellular calcium mobilization in rat mesangial cells.

We studied the effect of platelet-activating factor (PAF-acether) on rat mesangial cells (MC) and the intracellular mechanisms for PAF-acether-mediated MC activation. Contraction was measured as changes in planar cell surface area (PCSA), and intracellular free calcium concentration ([Ca2+]i) was measured as changes in the signal of the fluorescent indicator fura-2. PAF-acether induced a time- and dose-dependent reduction in PCSA and a dose-dependent increase in [Ca2+]i. Both phenomena were abolished by preincubation of the cells with the PAF-acether-binding blockers L652,731 and BN 52021. TMB-8, an inhibitor of intracellular calcium mobilization, partially inhibited both the reduction in PCSA and the increase in [Ca2+]i, whereas the Ca2+ entry blocker verapamil completely inhibited the reduction in PCSA but only partially blocked the increase in [Ca2+]i. Atrial natriuretic peptide (ANP) produced a dose-dependent inhibition of PAF-acether-induced cell contraction, but its effect was not statistically related to changes in [Ca2+]i. These results show that PAF-acether-induced MC contraction is associated with transient increases in [Ca2+]i, but the relaxing effects of ANP and verapamil may require additional physiologic interactions that involve mechanisms other than the [Ca2+]i transient.