Activation of particulate guanylyl cyclase by Vibrio vulnificus hemolysin

Citation
H. Kook et al., Activation of particulate guanylyl cyclase by Vibrio vulnificus hemolysin, EUR J PHARM, 365(2-3), 1999, pp. 267-272
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
EUROPEAN JOURNAL OF PHARMACOLOGY
ISSN journal
0014-2999 → ACNP
Volume
365
Issue
2-3
Year of publication
1999
Pages
267 - 272
Database
ISI
SICI code
0014-2999(19990122)365:2-3<267:AOPGCB>2.0.ZU;2-G
Abstract
Recently we reported that Vibrio vulnificus hemolysin, an exotoxin produced by V. vulnificus, dilates rat thoracic aorta via elevated cGMP levels with out affecting nitric oxide synthase. We investigated the mechanism further by observing the guanylyl cyclase activities in cytosolic, membrane, unfrac tionated, or reconstituted preparations. Hemolysin did not activate guanyly l cyclase in the membrane or cytosolic fraction, while it activated guanyly l cyclase in unfractionated or reconstituted preparation. The increased act ivity was not inhibited by the HS-142-1, a microbial polysaccharide which a ntagonizes atrial natriuretic peptide receptor, or 1H-[1,2,4]oxadiazolo[4,3 - alpha]quinoxalin-1-one (ODQ), a soluble guanylyl cyclase inhibitor. Howev er, it was attenuated by 6-(phenylamino)-5,8-quinolinedione (LY 83,583), wh ich inhibits the catalytic domain of both guanylyl cyclases, and by cholest erol, which blocks hemolysin-incorporation into the membrane. Removing ATP, a cofactor of particulate guanylyl cyclase, attenuated the activation and ATP gamma S, a non-phosphorylating analog, restored it. These results sugge st that V. vulnificus hemolysin activates particulate guanylyl cyclase via hemolysin incorporation into the vascular smooth muscle cell membrane in co operation with certain unidentified cytosolic component(s). (C) 1999 Elsevi er Science B.V. All rights reserved.