title: Uridine adenosine tetraphosphate induces contraction of circular and longitudinal gastric smooth muscle by distinct signaling pathways.
abstract: Extracellular nucleotides uridine-5'-triphosphate (UTP) and adenosine-5'-triphosphate (ATP) induce contraction of gastric smooth muscle (SM). The dinucleotide uridine adenosine tetraphosphate (Up4 A), an endothelium-derived contraction factor, induces vascular SM contraction. Its effect on gastric SM contractions, however, is unknown. We addressed the hypothesis that Up4 A induces gastric SM contraction via a mechanism that may differ between circular and longitudinal muscle (CM and LM, respectively). CM and LM were isolated from rat gastric fundus for the measurement of isometric tension. Up4 A induced transient contractile responses in both CM and LM, which were similar to those induced by ATP and UTP. Up4 A failed to induce contraction of either LM or CM in the absence of extracellular Ca(2+) or in the presence of nimodipine, an inhibitor of voltage-gated Ca(2+) channels. P2X1, 2, 4, 5 and 7 and P2Y1, 2, 4 and 6 receptor expression was detected in gastric SM by reverse transcription-polymerase chain reaction. IP5 I (a P2X receptor antagonist) and α,β-methylene-ATP (a P2X receptor agonist) had no effect on Up4 A-induced contractions of either LM or CM, and α,β-methylene-ATP alone failed to induce a contractile response in either tissue. Suramin (a P2Y receptor antagonist), on the other hand, significantly inhibited Up4 A-induced contraction of CM, but not LM. Up4 A-induced contraction of CM, but not LM, was also inhibited by pretreatment with Y-27632, an inhibitor of Rho-associated kinase. We conclude that Up4 A induces extracellular Ca(2+) -dependent contractions of rat gastric LM and CM, and Up4 A-induced contraction of CM is mediated by suramin-sensitive P2Y receptors and subsequent activation of the Rho-associated kinase pathway.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Nankai University, Tianjin, People' Republic of China.
authors.forename: Wensu
authors.initials: W
authors.lastname: Yuan
authors.forename: Zengyong
authors.initials: Z
authors.lastname: Wang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Deliang
authors.initials: D
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Bai
authors.forename: Michael P
authors.initials: MP
authors.lastname: Walsh
authors.forename: Yu
authors.initials: Y
authors.lastname: Gui
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000577:Amides / Q000008:administration & dosage; D000818:Animals; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism* / Q000502:physiology; D009924:Organ Culture Techniques; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D058470:Receptors, Purinergic P2Y / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013270:Stomach / Q000033:anatomy & histology / Q000502:physiology*; D013498:Suramin / Q000008:administration & dosage; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000577:Amides; D015226:Dinucleoside Phosphates; D011725:Pyridines; D058470:Receptors, Purinergic P2Y; C529314:uridine adenosine tetraphosphate; C108830:Y 27632; D013498:Suramin; D000255:Adenosine Triphosphate