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
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.