Parathyroid hormone-related protein inhibits indothelin-1 production
Jiang, B.; Morimoto, S.; Fukuo, K.; Hirotani, A.; Tamatani, M.; Nakahashi, T.; Nishibe, A.; Niinobu, T.; Hata, S.; Chen, S.; Ogihara, T.
Hypertension 27(3 Pt 1): 360-363
1996
ISSN/ISBN: 0194-911X PMID: 8698438 Document Number: 455580
The effect of human parathyroid hormone-related protein, a powerful vasodilator, on endothelin-1 production in cultured bovine pulmonary arterial endothelial cells was studied. Treatment with parathyroid hormone-related protein(134) at concentrations of 10-9 to 10-6 mol/L for 24 hours caused dose-dependent suppression of the secretion of endothelin-1, with maximal suppression at 10-7 mol/L to 74% of the control value. This inhibitory effect was completely abolished by coincubation with 100 ng/mL pertussis toxin. an inhibitor of GTP binding protein. Furthermore, addition of N-G-monomethyl-L-arginine, an inhibitor of nitric oxide synthase, at 10-3 mol/L significantly blocked the suppressive effect of parathyroid hormone-related protein(1-34) on endothelin-1 secretion, and further addition of 5 times 10-3 mol/L-arginine significantly attenuated the blocking effect of N-G-monomethyl-L-arginine. Para-thyroid hormone-related protein(1-34) at 10-7 mol/L resulted in an approximately fivefold increase in intracellular cGMP level. Northern blot analysis revealed that parathyroid hormone-related protein(1-34) inhibited both basal and thrombin-induced endothelin-1 gene expression. These findings suggest that the vasodilating property of parathyroid hormone-related protein may be mediated in part through its inhibitory effect on endothelin-1 production, which is probably mediated through nitric oxide and cGMP in endothelial cells. Thus, a feedback regulatory mechanism may exist between parathyroid hormone-related protein and endothelin-1 in the vascular wall.