SQ22536 and W-7 inhibit forskolin-induced cAMP elevation but not relaxation in newborn ovine pulmonary veins

Authors
Citation
Ys. Gao et Ju. Raj, SQ22536 and W-7 inhibit forskolin-induced cAMP elevation but not relaxation in newborn ovine pulmonary veins, EUR J PHARM, 418(1-2), 2001, pp. 111-116
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
EUROPEAN JOURNAL OF PHARMACOLOGY
ISSN journal
0014-2999 → ACNP
Volume
418
Issue
1-2
Year of publication
2001
Pages
111 - 116
Database
ISI
SICI code
0014-2999(20010420)418:1-2<111:SAWIFC>2.0.ZU;2-M
Abstract
The role of cAMP in forskolin-induced relaxation was studied in isolated pu lmonary veins of newborn Iambs (7-12 days). In vessels preconstricted with endothelin-1, forskolin at concentrations less than or equal to 10(-7) ICI had no effect on cAMP content and adenylyl cyclase activity but caused up t o 50% relaxation. At higher concentrations, forskolin markedly elevated c,c AMP content and adenylyl cyclase activity and caused a further relaxation. SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine; an adenylyl cyclase inh ibitor] and W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide; a calmo dulin-dependent adenylyl cyclase inhibitor] had no significant effect on fo rskolin-induced relaxation but markedly inhibited the elevation of cAMP con tent and adenylyl cyclase activity caused by forskolin. Rp-8-CPT-cAMPS [8-( 4-chlorophenylthio)-adenosine-3 ' ,5 ' -cyclic monophosphorothioate: an inh ibitor of cAMP-dependent protein kinases] and Rp-8-Br-PET-cGMPS (beta -phen yl-1, N-2-etheno-8-bromoguanosine-3 ' ,5 ' -cyclic monophosphorothioate; an inhibitor of cGMP-dependent protein kinases) attenuated the relaxation cau sed by a cAMP analog but not that caused by forskolin. These results sugges t that cAMP may not play a major role in forskolin-induced relaxation of pu lmonary veins of newborn lambs. (C) 2001 Published by Elsevier Science B.V.