Compounds increasing cAMP levels

Overview of compounds that increase intracellular cAMP levels, including their primary pharmacological action, effects on ABCA1 and ABCG1 expression (arrows: mRNA, protein), and effects on cellular cholesterol efflux. Effects on ABCA1, ABCG1, and cholesterol efflux are presented as follows: (↓) decreased; (= ) no effect; (↑) increased. Italicized symbols indicate changes in ABCA1 and ABCG1 mRNA levels, whereas nonitalicized symbols indicate protein levels.

CompoundPrimary ActionABCA1ABCG1Cholesterol EffluxReference
6-Benz-cAMPPKA agonistTHP-1THP-1Bingham et al., 2010
8-Bromo-cAMPcAMP analog=Skin fibroblastsaTHP-1Haidar et al., 2002; Lin and Bornfeldt, 2002
PMSkin fibroblastsa
8-(4-Chlorophenylthio)adenosine-cAMPcAMP analogJ774.A1=THP-1Sakr et al., 1999; Kellner-Weibel et al., 2003
L cells
=Skin fibroblastsa
Mouse PM
8-pcPT-2′-O-Me-cAMPEpac agonistTHP-1THP-1Bingham et al., 2010
ATL313A2AR agonistTHP-1THP-1Voloshyna et al., 2013
(Bu)2cAMPcAMP analogRAW264.7RAW264.7Manna et al., 2015
CGS-21680A2AR agonistTHP-1THP-1THP-1Bingham et al., 2010; Voloshyna et al., 2013
CilomastPDE4 inhibitorTHP-1THP-1Lin and Bornfeldt, 2002
CilostazolPDE3 inhibitorTHP-1THP-1THP-1Nakaya et al., 2010
=Small intestineb
Dibutyrl cyclic AMPcAMP analogRAW264Monocyte-derived macropaRAW264.7Abe-Dohmae et al., 2000; Gaidarov et al., 2013
Monocyte-derived macropaMonocyte-derived macropa
Doxazosinα-A1 adrenergic receptor antagonistTHP-1THP-1Iwamoto et al., 2007; Tsunemi et al., 2014
NCTC clone 1469
ForskolinAdenylyl cyclase activatorSkin fibroblastsaTHP-1Haidar et al., 2002; Lin and Bornfeldt, 2002
Skin fibroblastsa
H89PKA inhibitorCHO-K1 ABCG1(+12)CHO-K1 ABCG1(+12)Gelissen et al., 2012
=CHO-K1 ABCG1(−12)=CHO-K1 ABCG1(−12)
IBMXNonselective PDE inhibitorTHP-1Haidar et al., 2002; Lin and Bornfeldt, 2002
Skin fibroblastsa
KT5720PKA inhibitorCHO-K1 ABCG1(+12)Gelissen et al., 2012
=CHO-K1 ABCG1(−12)
MethotrexateDihydrofolate reductase inhibitorPBMCsaChen et al., 2011a
RolipramPDE4-selective inhibitorTHP-1THP-1Lin and Bornfeldt, 2002
  • IBMX, 3-isobutyl-1-methylxanthine; macrop, macrophage; MDM, monocyte-derived macrophage; PBMC, peripheral blood mononuclear cell; PM, peritoneal macrophages.

  • a Human.

  • b C57BL/6 mice.