ROLE OF PARATHYROID HORMONE-RELATED PROTEIN IN THE PROLIFERATION OF VASCULAR SMOOTH-MUSCLE CELLS

Human parathyroid hormone-related protein(1-34) [hPTHrP(1-34)] inhibit ed [H-3]thymidine incorporation into DNA of cultured vascular smooth m uscle 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 t heir antagonists, hPTHrP(7-34) and hPTH(3-34), showed no effect on VSM C DNA synthesis. The inhibitory effect of PTHrP on VSMC DNA synthesis was mimicked by dibutyryl-cAMP but not by dibutyryl-cGMP. These result s 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.