The role of tyrosine kinase in prostaglandin E2 and vanadate-evoked contractions in rabbit duodenum in vitro.
Prostaglandin E2 (PGE2) can interact with at least four cell surface receptors (EP1-EP4) in smooth muscle, which evokes a variety of intracellular responses depending on the G protein to which the cell surface receptors are coupled. The activation of G protein-coupled receptors and receptor tyrosine kinases can lead to the phosphorylation of tyrosine residues of various cellular proteins. The aim of this study was to examine the role of tyrosine phosphorylation in PGE2, vanadate and carbachol-evoked contractions. PGE2, vanadate, and carbachol induced contractile motor responses in the longitudinal smooth muscle of rabbit duodenum. PGE2-evoked contractions decreased in the presence of genistein or tyrphostin B44. PGE2-evoked contractions increased in the presence of vanadate. Vanadate-evoked contractions decreased in the presence of genistein. In contrast, tyrphostin 47 increased the vanadate-evoked contractions. Vanadate-evoked contractions were reduced in the presence of Ca2+-free solutions, verapamil, or indomethacin. U-73122 decreased PGE2-evoked contractions. Carbachol-evoked contractions decreased in the presence of genistein, tyrphostin B44 or tyrphostin 47. Our results suggest that PGE2, vanadate or carbachol-evoked contractions are mediated by protein tyrosine phosphorylation. Protein tyrosine phosphorylation might cause an increase in calcium influx through voltage-dependent channels and the release of prostaglandins in the longitudinal smooth muscle of the rabbit duodenum.
Grasa
L
L
Departamento de Farmacología y Fisiología (Fisiología), Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet, 177. Zaragoza, 50013, Spain.
Arruebo
M P
MP
Plaza
M A
MA
Murillo
M D
MD
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects* / Q000502:physiology; D004963:Estrenes / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D011760:Pyrrolidinones / Q000494:pharmacology; D011817:Rabbits; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D004963:Estrenes; D011760:Pyrrolidinones; D020032:Tyrphostins; C100661:tyrphostin B44; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C060152:tyrphostin 47; D014638:Vanadates; D014443:Tyrosine; D002217:Carbachol; D014700:Verapamil; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D015232:Dinoprostone; D002118:Calcium; D007213:Indomethacin