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.
Jiang
B
B
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Morimoto
S
S
Fukuo
K
K
Yasuda
O
O
Chen
S
S
Ogihara
T
T
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D003995:Dibutyryl Cyclic GMP; D003994:Bucladesine; D004247:DNA; D000242:Cyclic AMP