title: Mechanism of SNAP potentiating antiproliferative effect of calcitonin gene-related peptide in cultured vascular smooth muscle cells.
abstract: We previously showed that CGRP inhibits cell proliferation which correlates with an elevation of cAMP levels in rabbit aortic vascular smooth muscle cells (VSMCs). The present study determined the effects of S-nitroso-N-acetylpenicillamine (SNAP, a nitric oxide donor) on CGRP-induced antiproliferative effects and cellular mechanism in cultured rabbit aortic VSMCs. The cells (in fifth-sixth passage) were exposed to 2.5% fetal bovine serum for 24 h in the presence or absence of SNAP, hCGRP or both.(3)H-thymidine incorporation was used to measure DNA synthesis. The results showed that SNAP (60-100 microm) significantly inhibited the proliferation and elevated cGMP levels in cultured rabbit aortic VSMCs. In combination, however, SNAP (30 microm) potentiated hCGRP (10-100 n m)-induced antiproliferation. SNAP (30 microm) and hCGRP (10-100 n m) or forskolin (10 microm), an activator of adenylate cyclase, caused more than additive cAMP elevations, but not cGMP elevations, in these cells. Quazinone, an inhibitor of cGMP-inhibited-phosphodiesterase (cGI-PDE, PDE3), or SNAP plus quazinone caused a similar potentiation as SNAP of the hCGRP-induced elevations of cAMP levels. The data indicate that SNAP-induced potentiation of CGRP's effects likely involves inhibition of cGI-PDE, thus allowing enhanced accumulation of cAMP that mediates the antiproliferative effects of hCGRP in cultured rabbit aortic VSMCs.
authors.affiliation: Institute of Vascular Medicine, Third Hospital, Beijing, 100083, P. R. of China. xwang@mail.bjmu.edu.cn
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Bai
authors.forename: R R
authors.initials: RR
authors.lastname: Fiscus
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004357:Drug Synergism; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D026423:S-Nitroso-N-Acetylpenicillamine; D013936:Thymidine / Q000378:metabolism
chemical_list: D003470:Culture Media; D020030:Nitric Oxide Donors; D005576:Colforsin; D026423:S-Nitroso-N-Acetylpenicillamine; D004247:DNA; D000242:Cyclic AMP; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D010396:Penicillamine; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide; D013936:Thymidine