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 < or =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)-9H-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 (beta-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.
Gao
Y
Y
Department of Pediatrics, Harbor-UCLA Medical Center, University of California, Los Angeles, School of Medicine, Torrance, CA 90509, USA. ygao@prl.humc.edu
Raj
J U
JU
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000378:metabolism / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005576:Colforsin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011667:Pulmonary Veins / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D012756:Sheep / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D019332:Endothelin-1; D013449:Sulfonamides; D013873:Thionucleotides; C098740:8-bromo-beta-phenyl-1,N(2)-ethenoguanosine 3',5'-cyclic monophosphorothioate; C017759:9-(tetrahydro-2-furyl)-adenine; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C017967:W 7; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006152:Cyclic GMP; D000225:Adenine