| 저자(한글) |
Kwon, Tae Hoon,Jung, Hyunwoo,Cho, Eun Jeong,Jeong, Ji Hoon,Sohn, Uy Dong |
| 초록 |
P2 receptors are membrane-bound receptors for extracellular nucleotides such as ATP and UTP. P2 receptors have been classified as ligand-gated ion channels or P2X receptors and G protein-coupled P2Y receptors. Recently, purinergic signaling has begun to attract attention as a potential therapeutic target for a variety of diseases especially associated with gastroenterology. This study determined the ATP and UTP-induced receptor signaling mechanism in feline esophageal contraction. Contraction of dispersed feline esophageal smooth muscle cells was measured by scanning micrometry. Phosphorylation of $MLC_{20}$ was determined by western blot analysis. ATP and UTP elicited maximum esophageal contraction at 30 s and $10{ mu}M$ concentration. Contraction of dispersed cells treated with $10{ mu}M$ ATP was inhibited by nifedipine. However, contraction induced by $0.1{ mu}M$ ATP, $0.1{ mu}M$ UTP and $10{ mu}M$ UTP was decreased by U73122, chelerythrine, ML-9, PTX and $GDP{ beta}S$ . Contraction induced by $0.1{ mu}M$ ATP and UTP was inhibited by $G{ alpha}i_3$ or $G{ alpha}q$ antibodies and by $PLC{ beta}_1$ or $PLC{ beta}_3$ antibodies. Phosphorylated $MLC_{20}$ was increased by ATP and UTP treatment. In conclusion, esophageal contraction induced by ATP and UTP was preferentially mediated by P2Y receptors coupled to $G{ alpha}i_3$ and $G{ alpha}q$ proteins, which activate $PLC{ beta}_1$ and $PLC{ beta}_3$ . Subsequently, increased intracellular $Ca^{2+}$ and activated PKC triggered stimulation of MLC kinase and inhibition of MLC phosphatase. Finally, increased $pMLC_{20}$ generated esophageal contraction. |
