Effects of urotensin II on intracellular pH regulation in cultured human internal mammary artery smooth muscle cells.
The Na(+)-H(+) exchanger (NHE) and the Na(+)-HCO3(-) co-transporter (NBC) have been confirmed as two major active acid extruders in many mammalian cells. Whether the NHE and NBC functional co-exist in human internal mammary artery smooth muscle cells (HIMASMCs) remains unclear. The aims of the present study were to investigate the acid-extruding mechanisms and to explore the effects of urotensin-II (U-II), a powerful vasoconstrictor, on pHi regulators in HIMASMCs. We investigated the changes of pHi by BCECF-fluorescence in HIMASMCs. We found that (a) two Na(+)-dependent acid extruders, i.e. NHE and NBC, functionally co-exist; (b) U-II (3-100 nM) induced a concentration-dependent intracellular acidosis; and (c) U-II (3-100 nM) caused a concentration-dependent increase on NHE activity, while decrease on NBC activity. In summary, we demonstrate for the first time that two acid-extruders, NHE and NBC, functionally co-exist in HIMASMCs. Moreover, U-II induces a concentration-dependent intracellular acidosis through the balanced effect of its effect on increasing NHE activity and decreasing NBC activity.
Department of Cardiovascular Surgery, Tri-Service General Hospital, Taipei, Taiwan.
Yi-Ting
YT
Tsai
Department of Cardiovascular Surgery, Tri-Service General Hospital, Taipei, Taiwan.
Chung-Yi
CY
Lee
Department of Pharmacology, National Defense Medical Center, Taipei City 114, Taiwan.
Chih-Chin
CC
Hsu
Department of General Surgery, Cheng-Hsieng General Hospital, Taipei, Taiwan.
Chung-Yi
CY
Chang
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan.
Ming-Kai
MK
Hsueh
Department of Pharmacology, National Defense Medical Center, Taipei City 114, Taiwan.
Eagle Yi-Kung
EY
Huang
Department of Cardiovascular Surgery, Tri-Service General Hospital, Taipei, Taiwan; Department of Pharmacology, National Defense Medical Center, Taipei City 114, Taiwan.
Chien-Sung
CS
Tsai
Department of Pharmacology, National Defense Medical Center, Taipei City 114, Taiwan. Electronic address: shloh@ndmctsgh.edu.tw.
Shih-Hurng
SH
Loh
D002478:Cells, Cultured; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008323:Mammary Arteries / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D014579:Urotensins / Q000494:pharmacology*
D014579:Urotensins; C029677:urotensin II
Fluorescent-BCECF; Human internal mammary artery smooth muscle cells; Intracellular pH; Na(+)–H(+) exchanger (NHE); Na(+)–HCO(3)(−) co-transporter (NBC); Urotensin-II (U-II)