Effect and mechanism of α1B-adrenoceptor on cell growth in DDT1 MF-2 / 中国药理学通报

ABSTRACT

AIM　DDT1 MF-2 hamster smooth muscle cells were used to investigate the role of α1B-adrenoceptor (AR) in the cell proliferation and its signaling pathway. METHODS　DNA synthesis was measured by ［3H］thymidine (TdR) incorporation and the cell cycle was determined by flow cytometry. The actions of several inhibitors and activators of second messenger on NE-induced DNA synthesis were investigated. RESULTS　NE (0.1～1 μmol*L-1) elicited significant concentration-dependent stimulation of DDT1 MF-2 cell proliferation. The proliferative effect caused by α1B-AR was blocked by PLC inhibitor (U73122, 10 μmol*L-1), Ca2+/ATPase inhibitor (cyclopiazonic acid, 10 μmol*L-1), intracellular Ca2+ chelator (BAPTA/AM, 10 μmol*L-1), PKC inhibitors (RO-31-8220, 0.1 μmol*L-1 and calphostin C, 0.1 μmol*L-1), TK inhibitors (tyrphostin A25, 10 μmol*L-1 and genistein, 10 μmol*L-1), and MEK1/2 inhibitor (PD 98059, 10 μmol*L-1). CONCLUSION　α1B-AR subtypes stimulate DDT1 MF-2 cells growth and its signal pathway is related to the PLC activation、Ca2+ release、PKC、TK and ERKs activation.