cAMP induces up-regulation of ETA receptor mRNA and increases responsiveness to endothelin-1 of rat aortic smooth muscle cells in primary culture.
The effects of cAMP on the expression of ETA (ET-1 selective type) receptor mRNA and on the response to endothelin-1 (ET-1) were investigated in rat aortic smooth muscle cells in primary culture, using reverse transcription polymerase chain reaction (RT-PCR) and fura-2 microfluorometry of cytosolic Ca2+ concentrations ([Ca2+]i). Incubation of the smooth muscle cells with 10 microM forskolin and 10 microM 3-isobutyl-1-methyl-xanthine (IBMX) induced an increase in ETA receptor mRNA by 420% of control after 24 hours. ET-1 induced a biphasic increase in [Ca2+]i, first transient and second sustained phases. Incubation of the smooth muscle cells with forskolin and IBMX for 24 hours increased the [Ca2+]i response by 849% in the first phase and 286% in the second phase, compared with time-matched controls. From these results, we conclude that cAMP induces an up-regulation of the ETA receptor mRNA and increases responsiveness to ET-1 of rat aortic smooth muscle cells in primary culture.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017466:Receptors, Endothelin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015183:Restriction Mapping; D015854:Up-Regulation / Q000187:drug effects
D016232:Endothelins; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D005576:Colforsin; D000242:Cyclic AMP; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine