Cyclic AMP calcium

Choi, M. S., and Cooke, B. A. (1992). Calmidazoliumis apotent stimulator of steroidogenesis via mechanisms not involving cyclic AMP, calcium or protein synthesis. Biochem J 281 (Pt 1), 291-296. 

Cyclic AMP Metabolism 530 Mode of Action of Cyclic AMP Calcium and Hormone Action 532 Conclusion 533... 

There are numerous second messenger systems such as those utilizing cyclic AMP and cyclic GMP, calcium and calmodulin, phosphoinosiddes, and diacylglerol with accompanying modulatory mechanisms. Each receptor is coupled to these in a variety of ways in different cell types. Therefore, it can be seen that it is impractical to attempt to quantitatively define each stimulus-response mechanism for each receptor system. Fortunately, this is not an... 

Second messenger, these are molecules produced by cellular effectors that go on to activate other biochemical processes in the cell. Some examples of second messengers are cyclic AMP, inositol triphosphate, arachidonic acid, and calcium ion (see Chapter 2.2). 

The steroid hormone 1,25-dihydroxy vitamin D3 (calcitriol) slowly increases both intestinal calcium absorption and bone resorption, and is also stimulated through low calcium levels. In contrast, calcitonin rapidly inhibits osteoclast activity and thus decreases serum calcium levels. Calcitonin is secreted by the clear cells of the thyroid and inhibits osteoclast activity by increasing the intracellular cyclic AMP content via binding to a specific cell surface receptor, thus causing a contraction of the resorbing cell membrane. The biological relevance of calcitonin in human calcium homeostasis is not well established. 

Protein kinase A (PKA) is a cyclic AMP-dependent protein kinase, a member of a family of protein kinases that are activated by binding of cAMP to their two regulatory subunits, which results in the release of two active catalytic subunits. Targets of PKA include L-type calcium channels (the relevant subunit and site of phosphorylation is still uncertain), phospholam-ban (the regulator of the sarcoplasmic calcium ATPase, SERCA) and key enzymes of glucose and lipid metabolism. 

Interaction of the food with the gastric mucosal layer is the normal trigger for gastric cells to release gastrin, which is then carried by the bloodstream to the parietal cells. Calcium ions and cyclic AMP act as intracellular messengers in the transfer of the signal from the receptors to the proton pumps of parietal cells where the acid is generated. 

Figure 6. A hypothetical scheme for the control of the number of active crossbridges in smooth muscle. Following the activation of a smooth muscle by an agonist, the concentrations of intermediates along the main route begins to build up transiently. This is shown by the thickened arrows. Also, cAMP is generated which is universally an inhibitor in smooth muscle. Cyclic AMP in turn combines with protein kinase A, which accounts for most of its action. The downstream mechanisms, however, are not well worked out and at least three possibilities are likely in different circumstances. First, protein kinase A is known to catalyze the phosphorylation of MLCK, once phosphorylated MLCK has a relatively lower affinity for Ca-calmodulin so that for a given concentration of Ca-calmodulin, the activation downstream is reduced. The law of mass action predicts that this inhibition should be reversed at high calcium concentrations. Other cAMP inhibitory mechanisms for which there is evidence include interference with the SR Ca storage system, and activation of a MLC phosphatase.

Katz, A. M., Tada, M., and Kirchberger, M. A. (1975) Control of calcium transport in the myocardium by the cyclic AMP-protein kinase system. In Advances in Cyclic Nucleotide Research, Vol. 5, edited by G. 1. Drummond, P. Greengard, and G. A. Robinson, pp. 453-472. Raven Press, New York. 

Table IX. Urinary Cyclic AMP and Hydroxyproline as Affected by Orthophosphate, Hexametaphosphate, and Calcium...

We have tested the hypothesis that insulin inhibits the stimulatory effect of parathyroid hormone (PTH) on calcium reabsorption in the distal nephron. PTH is known to enhance calcium transport in renal cells, probably by stimulation of adenylate cyclase and subsequent increases in 3 5 cyclic AMP productoin. Since insulin had been observed to inhibit PTH-stimulated increases in kidney cyclic AMP levels in vitro (24) we investigated whether insulin-mediated hypercalciuria was dependent on the presence of PTH in vivo. 

Mehorta and coworkers (1989) observed that isolated fractions of brain and heart cells from rats orally administered 0.5-10 mg endrin/kg showed significant inhibition of Ca+2 pump activity and decreased levels of calmodulin, indicating disruption of membrane Ca+2 transport mechanisms exogenous addition of calmodulin restored Ca+2-ATPase activity. In vitro exposure of rat brain synaptosomes and heart sarcoplasmic reticuli decreased total and calmodulin-stimulated calcium ATPase activity with greater inhibition in brain preparations (Mehorta et al. 1989). However, endrin showed no inhibitory effects on the calmodulin-sensitive calcium ATPase activity when incubated with human erythrocyte membranes (Janik and Wolf 1992). In vitro exposure of rat brain synaptosomes to endrin had no effect on the activities of adenylate cyclase or 3, 5 -cyclic phosphodiesterase, two enzymes associated with synaptic cyclic AMP metabolism (Kodavanti et al. 1988). 

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. 

The effect of sphingosine on other enzymes may also contribute to its apoptotic effect. These include the inhibition of calcium/calmodulin-requiring enzymes and DNA primase and the stimulation of casein kinase II and several unidentified kinases (Alessenko, 2000). In addition, sphingosine can increase the cellular concentration of cyclic AMP, which is inhibitory for proliferation in many cell types (Pyne and Pyne, 1996). 

There are several mechanisms whereby antidepressants can modify intracellular events that occur proximal to the posts)maptic receptor sites. Most attention has been paid to the actions of antidepressants on those pathways that are controlled by receptor-coupled second messengers (such as cyclic AMP, inositol triphosphate, nitric oxide and calcium binding). However, it is also possible that chronic antidepressant treatment may affect those pathways that involve receptor interactions with protein tyrosine kinases, by increasing specific growth factor synthesis or by regulating the activity of proinflammatory cytokines. These pathways are particularly important because they control many aspects of neuronal function that ultimately underlie the ability of the brain to adapt and respond to pharmacological and environmental stimuli. One mechanism whereby antidepressants could increase the s)mthesis of trophic factors is... 

The mechanism of action of these drugs is not completely understood. However, it is very likely that they inhibit cellular phosphodiesterase of the myocardium, which leads to an elevation in the cellular level of cyclic AMP, which in turn facihtates contraction of myocardial cells. It is clear that these drags are not 8-adrenoreceptor antagonists, and that their effect is not mediated by inhibition of (Na -K+) ATPase. They simultaneously increase the flow of calcium ions into the cell. They are used for short-term control of patients that inadequately react to cardiac glycosides, diuretics, and coronary vasodilating agents. 

BNST, bed nucleus of the stria terminalis CREB, cyclic AMP response element-binding protein CRH, corticotrophin-releasing hormone CS, conditioned stimuH GABA, y-aminobutyric acid GCC, voltage-gated calcium channels NE, norepinephrine NMDA, iST-methyl-D-aspartate PAG, periaqueductal gray. 

---