3 ,5 -AMP, cAMP

Smooth muscle contractions are subject to the actions of hormones and related agents. As shown in Figure 17.32, binding of the hormone epinephrine to smooth muscle receptors activates an intracellular adenylyl cyclase reaction that produces cyclic AMP (cAMP). The cAMP serves to activate a protein kinase that phosphorylates the myosin light chain kinase. The phosphorylated MLCK has a lower affinity for the Ca -calmodulin complex and thus is physiologically inactive. Reversal of this inactivation occurs via myosin light chain kinase phosphatase. 

Cyclic AMP (cAMP) (Figure 18-5) is formed from ATP by adenylyl cyclase at the inner surface of cell membranes and acts as an intracellular second messenger in response to hormones such as epinephrine, norepinephrine, and glucagon. cAMP is hydrolyzed by phosphodiesterase, so terminating hormone action. In hver, insulin increases the activity of phosphodiesterase. 

There are many examples of phosphorylation/dephosphorylation control of enzymes found in carbohydrate, fat and amino acid metabolism and most are ultimately under the control of a hormone induced second messenger usually, cytosolic cyclic AMP (cAMP). PDH is one of the relatively few mitochondrial enzymes to show covalent modification control, but PDH kinase and PDH phosphatase are controlled primarily by allosteric effects of NADH, acetyl-CoA and calcium ions rather than cAMP (see Table 6.6). 

There seems to be no metabolic control exerted on hepatic 25-hydroxylase and so all of the available cholecalciferol is converted. Hydroxylation in the kidney however is an important control point being regulated by PTH, and indirectly therefore by calcium and phosphate concentrations. Stimulation of la-hydroxylase by PTH is via a cyclic AMP (cAMP) -dependent mechanism and longer-term regulation of the activity of this enzyme is via induction mediated by other hormones such as oestrogens, cortisol and growth hormone. Typically, the plasma concentration of 1,25 dihydroxy vitamin D is in the range 20-60 ng/1, that is approximately 1000-times lower than that of its precursor. 

Sequence of Events From Receptor to Protein Kinase Cyclic AMP (cAMP) and Phosphatidylinositol Bisphosphate (PIP )... 

Cyclic AMP, cAMP, is perhaps the most important signaling molecule in human biochemistry. 

Adenylate cyclase the enzyme that catalyzes the formation of cyclic AMP (cAMP). 

The level of cyclic AMP (cAMP) is increased by nitrogen starvation this triggers expression of ligninolytic activity and veratryl alcohol biosynthesis (40). 

The enzyme phosphodiesterase (type III) catalyzes the biode-gradation of cyclic AMP (cAMP). Inhibition of this enzyme will cause accumulation of the nucleotide cAMP and hence induces an increase in cardiac contractile force. This effect does not involve cardiac jS-adrenoceptors and will therefore persist after downregulation of these receptors associated with heart failure. 

The metabotropic glutamate receptor family includes at least seven different types of G protein-coupled receptors (mGluRj 7). These are linked to different second messenger systems and lead to the increase of intracellular Ca or the decrease of cyclic AMP (cAMP). The increase of intracellular Ca leads to the phosphorylation of target proteins in the cell. 

The nature of the second messenger response to a given neurotransmitter depends on the subtype of receptor to which it binds and the G protein to which the receptor is coupled. Three of the most commonly utilized G proteins include G, which stimulates adenylyl cyclase to produce cyclic AMP (cAMP) Gj, which inhibits adenylyl cyclase, resulting in lower intracellullar levels of cAMP and Gq, which activates phospholipase C to produce the second messengers IP3 and DAG. In general, these activities refer to the function of the a subunit however, it should be pointed out that the py complex has its own set of activities (on adenylyl cyclase, phospholipase C, channels, mitogen-activated protein kinase [MAPK]) that are just now becoming better clarified. 

Direct effects of oximes on the gastrointestinal tract are related entirely to the route of administration—they are seen only after oral administration. Ingestion of tablets of 2-PAM or related salts is often accompanied by transient diarrhea and cramps. The full explanation is not known. In the case of P2S, it has been suggested that a dose of 20 mg/kg inhibits ATPase and therefore produces excess Intestinal fluid and diarrhea. The effect depends on concentration and is reversible. 2-PAM has no effect on cyclic AMP (cAMP), adenylate cyclase, or phosphodiesterase. 

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