Role of parathyroid hormone-related protein in the proliferation of vascular smooth muscle cells.

Human parathyroid hormone-related protein(1-34) [hPTHrP(1-34)] inhibited [3H]thymidine incorporation into DNA of cultured vascular smooth muscle cells (VSMC) and increased intracellular cAMP accumulation, both in a concentration-dependent manner. The potency of hPTHrP(1-34) was similar to that of human parathyroid hormone(1-34) [hPTH(1-34)], but their antagonists, hPTHrP(7-34) and hPTH(3-34), showed no effect on VSMC DNA synthesis. The inhibitory effect of PTHrP on VSMC DNA synthesis was mimicked by dibutyryl-cAMP but not by dibutyryl-cGMP. These results suggest that PTHrP, as an autocrine and/or paracrine regulator, may inhibit VSMC DNA synthesis mediated at least partly by cAMP, a second messenger which has also been proposed to mediate vascular relaxation.