Urotensin II receptor in the rat airway smooth muscle and its effect on the rat airway smooth muscle cells proliferation.
OBJECTIVE
To investigate the characteristics of urotensin II (U-II) receptor in the rat airway smooth muscle and the effect and signal transduction pathway of U-II on the proliferation of airway smooth muscle cells.


METHODS
Using 125I-UII binding assay to measure the Bmax and Kd of U-II receptor. Using the 3H-TdR incorporation to determine the effect of U-II on the proliferation of airway smooth muscle cells and its signal transduction pathway. Using Fura-2/AM to measure the effect of U-1I on the cytosolic free calcium concentration.


RESULTS
1. 125I-UII binding increased with the time and reached saturation at 45 min. The B(max0 was (11.36 +/- 0.37)fmol/mg pr and Kd was (4.46 +/- 0.61) nmol/L. 2. U-II increased 3H-TdR incorporation of the airway smooth muscle cells in a dose-dependent manner. 3. H7, PD98059 and nicardipine, inhibitors of PKC, MAPK, calcium channel, respectively, significantly inhibited U-II-stimulated 3H-TdR incorporation of airway smooth muscle cells. W7, inhibitor of CaM-PK, had no effect. 4. Cyclosporin A, inhibitor of CaN, inhibited 3H-TdR incorporation of the airway smooth muscle cells induced by U-II in a dose-dependent manner. 5. U-II promoted cytosolic free calcium concentration increase by 18%.


CONCLUSIONS
1. There was U-II receptor in the rat airway smooth muscle. 2. The effect of U-II-stimulated 3H-TdR incorporation of airway smooth muscle cells was mediated by such signal transduction pathway as Ca2+, PKC, MAPK and CaN, etc.
Chen
Y
Y
Respiratory Department, Third Hospital, Peking University, Beijing 100083. redasia@sina.com
Zhao
M
M
Liu
X
X
Yao
W
W
Yang
J
J
Zhang
Z
Z
Tang
C
C
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009130:Muscle, Smooth / Q000737:chemistry*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000032:analysis*; D015398:Signal Transduction; D014132:Trachea / Q000737:chemistry; D014579:Urotensins / Q000494:pharmacology*
D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C473142:Uts2r protein, rat; C029677:urotensin II; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium