Adenylyl cyclase: cAMP pathway : General Pharmacology Notes

Adenylyl cyclase: cAMP pathway Activation of AC results in intracellular accumulation
of second messenger cAM P (Fig. 4.6) which functions mainly through cAMP-dependent
protein kinase (PKA).

The PKA phosphorylates and alters the functi on of many enzymes, ion
channels, transporters. transcription factors and structural proteins to manifest as increased
contractility/impulse generation (heart), relaxation (smooth muscle), glycogenolysis, lipolysis,
inhibition of secretion/mediator release, modulation of junctional transmission, water conservation
by kidney, steroid hormone synthesis, etc.

In addition, cAMP directly opens a specific type of membrane Ca2 + channel called cyclic nucleotide
gated channel (CNG) in the heart, brain and kidney. The other mediators of cellular actions
of cAMP are: cAMP response element binding protein (CREB) which is a transcription factor,
cAM P regulated guanine nucleotide exchange factors called EPACs and certain transporters.
Responses opposite to the above are produced when AC is inhibited through inhibitory Gi-protein.
The action of cAMP is terminated intracellularly by phosphodiesterases (PDEs) which
hydrolyse it to 5-A MP. Some isoforms of PDE (PDE3 , PDE4 ) are selective for cAMP, while
PDE5 is selective for cGMP