title: Inhibition of untransformed prostaglandin H(2) production and stretch-induced contraction of rabbit pulmonary arteries by indoxam, a selective secretory phospholipase A(2) inhibitor.
abstract: Involvement of secretory phospholipase A(2) (sPLA(2)) in the stretch-induced production of untransformed prostaglandin H(2) (PGH(2)) in the endothelium of rabbit pulmonary arteries was investigated. The stretch-induced contraction was significantly inhibited by indoxam, a selective inhibitor for sPLA(2), and NS-398, a selective inhibitor for cyclooxygenase-2 (COX-2). Indoxam inhibited the RGD-sensitive-integrin-independent production of untransformed PGH(2), but did not affect the RGD-sensitive-integrin-dependent production of thromboxane A(2) (TXA(2)). These results suggest that the stretch-induced contraction and untransformed PGH(2) production was mediated by sPLA(2)-COX-2 pathway, making it a new possible target for pharmacological intervention of pulmonary artery contractility.
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Iwate Medical University, Japan. ytanabe@iwate-med.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Maki
authors.initials: M
authors.lastname: Saito
authors.forename: Yuki
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Akihisa
authors.initials: A
authors.lastname: Kamataki
authors.forename: Takashi
authors.initials: T
authors.lastname: Sawai
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hirose
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D002219:Carbamates / Q000494:pharmacology*; D002478:Cells, Cultured; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007212:Indolizines / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects* / Q000502:physiology; D009578:Nitrobenzenes / Q000494:pharmacology; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors*; D044262:Prostaglandin H2 / Q000096:biosynthesis*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology*; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000096:biosynthesis
chemical_list: D002219:Carbamates; D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D007212:Indolizines; D009578:Nitrobenzenes; D013449:Sulfonamides; C119389:indoxam; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D044262:Prostaglandin H2; D013928:Thromboxane A2; D054497:Phospholipases A2, Secretory