Receptor-mediated mitogenic effects of substance P on cultured smooth muscle cells

The neuropeptide substance P, a known mitogen for human blood T-lymphocytes, now is shown to stimulate proliferation of embryonic rat aortic smooth muscle cells of the A7r5 line, at concentrations of 10(-9) M to 10(-6) M. Neurotensin (NT), that has vascular and smooth muscle activity similar to SP, failed to induce proliferation of A7r5 cells. At proliferation-enhancing concentrations, SP increased the concentration of cytosolic Ca2+ in A7r5 cells, suggesting activation of the phosphatidylinositol pathway. Binding of [125I]-substance P to A7r5 cells reached equilibrium rapidly at 4 degrees C, and was saturable, implying that the activation of smooth muscle cells by SP is a receptor-mediated process.