cAMP
The “second messenger” archetype cAMP is one of the most important cellular signalling molecules with central functions including the regulation of insulin and glucagon secretion from the pancreatic β- and α-cells, respectively. cAMP is generated from ATP by adenylyl cyclases (ACs), an enzyme family with ten members many of which are expressed in islet cells(see also reviews). All but one isoform is regulated by G-protein coupled receptors that either mediate stimulation via Gαs or suppression via Gαi subunits. Some of these ACs are also activated or inhibited by Ca2+/calmodulin and phosphorylation by protein kinases.
The Ca2+-stimulated isoforms AC1, AC3 and AC8, as well as the Ca2+-insensitive AC9 have been found important in rodent β-cells and insulinoma cells. Less is known about human β-cells but the Ca2+- and protein kinase A (PKA)-inhibited AC5 was recently found critical for glucose stimulation of insulin secretion. The concentration of cAMP is also regulated at the level of degradation by cyclic nucleotide phosphodiesterases (PDEs), which catalyse the hydrolysis of cAMP to 5’-AMP. The actions of cAMP are mediated via PKA and the guanine nucleotide exchange protein directly activated by cAMP (Epac). PKA is a well characterized heterotetramer composed of two regulatory subunits and two catalytic subunits. Epac is a guanine nucleotide exchange factor for Rap GTPases that has lower affinity for cAMP than PKA. There are two isoforms, Epac1 and Epac2 with three alternatively spliced forms of the latter.
References
1.Tengholm A,et al. Diabetes Obes Metab. 2017;19 Suppl 1:42–53.
The Ca2+-stimulated isoforms AC1, AC3 and AC8, as well as the Ca2+-insensitive AC9 have been found important in rodent β-cells and insulinoma cells. Less is known about human β-cells but the Ca2+- and protein kinase A (PKA)-inhibited AC5 was recently found critical for glucose stimulation of insulin secretion. The concentration of cAMP is also regulated at the level of degradation by cyclic nucleotide phosphodiesterases (PDEs), which catalyse the hydrolysis of cAMP to 5’-AMP. The actions of cAMP are mediated via PKA and the guanine nucleotide exchange protein directly activated by cAMP (Epac). PKA is a well characterized heterotetramer composed of two regulatory subunits and two catalytic subunits. Epac is a guanine nucleotide exchange factor for Rap GTPases that has lower affinity for cAMP than PKA. There are two isoforms, Epac1 and Epac2 with three alternatively spliced forms of the latter.
References
1.Tengholm A,et al. Diabetes Obes Metab. 2017;19 Suppl 1:42–53.
GPCR/G Protein
ACAT(3)
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Bombesin Receptor(11)
Bradykinin Receptor(18)
Calcium Channel(137)
cAMP(9)
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CaSR(17)
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FFAR(5)
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Leukotriene Receptor(9)
LHR(1)
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Neurokinin Receptor(34)
Neuropeptide Y Receptor(36)
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SGLT(22)
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cAMP
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Atherosperminine
catalog no : M29285
cas no: 5531-98-6
Atherosperminine shows cholinesterase inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Atherosperminine exerts a non-specific relaxant effect on the trachealis, its major mechanism of action appears to be inhibition of cAMP phosphodiesterase. -
ESI-08
catalog no : M26208
cas no: 301177-43-5
ESI-08 is an effective antagonist of EPAC2 with an IC50 of 8.4 μM. ESI-08 selectively blocks cAMP-induced EPAC activation but not cAMP-mediated PKA activation. -
EPAC 5376753
catalog no : M26202
cas no: 302826-61-5
EPAC 5376753 is an allosteric inhibitor of EPAC1 with an IC50 of 4 μM in Swiss 3T3 cells. -
CE3F4
catalog no : M23602
cas no: 143703-25-7
CE3F4 is a selective antagonist of exchange protein directly activated by cAMP. -
ESI-05
catalog no : M22840
cas no: 5184-64-5
ESI-05 is a specific EPAC2 (exchange protein directly activated by cAMP 2) antagonist (IC50: 0.4 μM). ESI-05 inhibits cAMP-mediated activation of EPAC2, as well as EAPC2, mediated Rap1 activation.