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

The role of cAMP in forskolin-induced relaxation was studied in isolated pulmonary veins of newborn lambs (7–12 days). In vessels preconstricted with endothelin-1, forskolin at concentrations ≤10 −7 M had no effect on cAMP content and adenylyl cyclase activity but caused up to 50% relaxation. At hig...

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Veröffentlicht in:European journal of pharmacology 2001-04, Vol.418 (1), p.111-116
Hauptverfasser: Gao, Yuansheng, Raj, J.Usha
Format: Artikel
Sprache:eng
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Zusammenfassung:The role of cAMP in forskolin-induced relaxation was studied in isolated pulmonary veins of newborn lambs (7–12 days). In vessels preconstricted with endothelin-1, forskolin at concentrations ≤10 −7 M had no effect on cAMP content and adenylyl cyclase activity but caused up to 50% relaxation. At higher concentrations, forskolin markedly elevated cAMP content and adenylyl cyclase activity and caused a further relaxation. SQ22536 [9-(tetrahydro-2-furanyl)-9 H-purin-6-amine; an adenylyl cyclase inhibitor] and W-7 [ N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide; a calmodulin-dependent adenylyl cyclase inhibitor] had no significant effect on forskolin-induced relaxation but markedly inhibited the elevation of cAMP content and adenylyl cyclase activity caused by forskolin. Rp-8-CPT-cAMPS [8-(4-chlorophenylthio)-adenosine-3′,5′-cyclic monophosphorothioate; an inhibitor of cAMP-dependent protein kinases] and Rp-8-Br-PET-cGMPS (β-phenyl-1, N 2-etheno-8-bromoguanosine-3′,5′-cyclic monophosphorothioate; an inhibitor of cGMP-dependent protein kinases) attenuated the relaxation caused by a cAMP analog but not that caused by forskolin. These results suggest that cAMP may not play a major role in forskolin-induced relaxation of pulmonary veins of newborn lambs.
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(01)00929-3