Cyclic AMP function

It has been suggested139 that adenosine 3 5 -monophosphate (cyclic AMP) functions as an intracellular second messenger which mediates the effects of specific hormones on their target cells. According to this concept, a hormone such as... 

Adenylyl cyclase is the effector enzyme that synthesizes cyclic adenosine monophosphate (cAMP) from ATP. Cyclic AMP functions as a second messenger to relay extracellular signals to intracellular enzymes such as protein kinase A. Adenylyl cyclases are integral membrane proteins that... 

In most cases, cyclic AMP functions by activating the isoforms of cyclic AMP-dependent protein kinase (PKA), and cyclic GMP activates a PKG. Recently, a number of additional actions of cyclic nucleotides have been described, all with pharmacological relevance. 

Many biochemical and biophysical studies of CAP-DNA complexes in solution have demonstrated that CAP induces a sharp bend in DNA upon binding. This was confirmed when the group of Thomas Steitz at Yale University determined the crystal structure of cyclic AMP-DNA complex to 3 A resolution. The CAP molecule comprises two identical polypeptide chains of 209 amino acid residues (Figure 8.24). Each chain is folded into two domains that have separate functions (Figure 8.24b). The larger N-terminal domain binds the allosteric effector molecule, cyclic AMP, and provides all the subunit interactions that form the dimer. The C-terminal domain contains the helix-tum-helix motif that binds DNA. 

Depletion of ATP in the cells prevents maintenance of the membrane potential, inhibits the functioning of ion pumps, and attenuates cellular signal transduction (e.g., formation of second messengers such as inositol phos phates or cyclic AMP). A marked ATP depletion ultimately impairs the activ-itv of the cell and leads to ceil death. 

FIGURE 2.17 Differential efficiency of receptor coupling for cardiac function, (a) Guinea pig left atrial force of contraction (inotropy, open circles) and rate of relaxation (lusitropy, filled circles) as a function (ordinates) of elevated intracellular cyclic AMP concentration (abscissae). Redrawn from [6]. 

Cyclic nucleotides (cAMP and cGMP) are formed enzymatically from the corresponding triphosphates. As ubiquitous second messengers, they mediate many cellular functions which are initiated by first (extracellular) messengers. Their prime targets in eucaryotic cells are protein kinases ( cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase), ion channels and ensymes. 

TO Mjorndal, SE Chesrown, MJ Frey, BR Reed, WM Gold. (1978). Effect of increased cyclic AMP on antigen-induced mediator release and function in canine lung in vivo. Clin Res 26 539A. 

Terwilliger, R.Z., Beitner-Johnson, D., Sevarino, K.A., Crain, S.M., Nestler, E.J. A general role for adaptations in G-proteins and the cyclic AMP system in mediating the chronic actions of morphine and cocaine on neuronal function. Brain Res. 548 100, 1991. 

Cyclic AMP can be viewed as subserving two major functions in the nervous system 375... 

Most of the effects of cyclic AMP on cell function are mediated via protein phosphorylation 375... 

Cyclic AMP can be viewed as subserving two major functions in the nervous system. First, cAMP mediates some short-term aspects of synaptic transmission some rapid actions of certain neurotransmitters on ion channels that do not involve ligand-gated channels are mediated through cAMP. 

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