Cyclic AMP concentration

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]. 

Insulin and glucagon regulate gluconeogenesis via changes in cyclic AMP concentration. 

An increase in cyclic AMP concentration activates protein kinase-A. The latter phosphorylates the following enzymes, which leads to an increase in the rate of gluconeogenesis. 

Figure 7.15 Inhibition of acetyl-CoA carboxylase by cyclic AMP dependent protein kinase and AMP dependent protein kinase the dual effect of glucagon. Phosphorylation of acetyl-CoA carboxylase by either or both enzymes inactivates the enzyme which leads to a decrease in concentration of malonyl-CoA, and hence an increase in activity of carnitine palmitoyltransferase-I and hence an increase in fatty acid oxidation. Insulin decreases the cyclic AMP concentration maintaining an active carboxylase and a high level of malonyl-CoA to inhibit fatty acid oxidation.

Figure 14.13 The kinetic sequence of reactions that control the cyclic AMP concentration, and its binding to the effector system, and the kinetic sequence that controls the concentration of a neurotransmitter and its binding to the receptor on the postsyn-aptic membrane. Processes (1) are reactions catalysed by adenyl cyclase, and exocytosis. Reactions (2) are catalysed by phosphodiesterase and, for example, acetylcholinesterase. Reactions (3) are the interactions between the messenger and the effector system both the latter are equilibrium binding processes. (See Chapter 12 (p. 266) for discussions of equilibrium binding.)...

Some, but not all, of the pharmacological effects of eicosanoids are mediated through alterations in the concentration of cyclic adenosine monophosphate (cyclic AMP). For example, prostaglandins Ej and E2 inhibit platelet aggregation by increasing the cyclic AMP concentration. Conversely,... 

As illustrated in Fig. 3A, dopamine leads to a 30% (p <0.01) inhibition of basal cyclic AMP levels in pars intermedia cells at an EDgg value of 5.0 nM. An almost identical potency of dopamine is observed on the elevated cyclic AMP concentration induced by simultaneous incubation with 30 nM (-)isoproterenol (Fig. 3B). Similar inhibitory effects of dopamine are observed in the presence of a phosphodiesterase inhibitor, isobutylmethylxanthine, thus... 

In the liver, isoprenaline-stimulated adenylate cyclase has been found to be located almost exclusively on the surface of the parenchymal cells, with little or no deposit on the surface of the reticulo-endothelial cells. In contrast, the predominant effect of glucagon resulted in the deposition of reaction product on the reticulo-endothelial cell surface, although deposits were also present on the parenchymal cells. In the presence of F , there were substantial deposits on the surface of both types of cells. These results demonstrate that distinct enzyme systems are present in parenchymal and reticulo-endothelial cells. No theories concerning the function of adenylate cyclase in the liver have considered its role in the endothelial cells which act mainly on phagocytes. These cells contribute 35% of the cells in the liver and can be expected to contribute substantially to biochemical measurements of adenylate cyclase activity and cyclic AMP concentrations when liver slices, homogenates, or cell fractions constitute the enzyme source. 

Hence the action of thromboxane-A lowers cyclic AMP concentration and promotes platelet adhesion prostacyclin raises cyclic AMP concentration and prevents platelet adhesion. 

Dipyridamole reversibly inhibits platelet phosphodiesterase (see Fig. 28.3) and in consequence cyclic AMP concentration is increased and platelet (thrombotic) reactivity reduced evidence also suggests that its antithrombotic effect may derive from release of prostaglandin precursors by vascular endothelium. Dipyridamole is extensively bound to plasma proteins and has a t/ of 12 h. 

AminophyUme facilitates neuromuscular transmission, perhaps by increasing neurotransmitter release, through raising cyclic AMP concentrations at the neuromuscular junction via phosphodiesterase inhibition (37). This would account for the antagonism of pancuronium-induced blockade that has been reported in the presence of very high serum concentrations of theophylline (38). 

Pentoxifylline (oxipentifylline) is a methylxanthine that antagonizes the vasoconstrictor effects of catecholamines and increases cyclic AMP concentrations, causing smooth muscle to relax. It has also been claimed to correct impaired microcirculation, by improving various factors that disturb blood rheology, and to reduce the generation of toxic free radicals from leukocytes during ischemic leg exercise in patients with intermittent claudication. Pentoxifylline has been used to suppress overproduction of tumor necrosis factor alfa in conditions such as falciparum malaria and rheumatoid arthritis and in transplant recipients, with varied success. 

Four hundred adults presenting with acute watery diarrhea were entered into a randomized, placebo controlled, double blind clinical trial of berberine, tetracycline, and tetracycline + berberine to study the antisecretory and vibriostatic effects of the alkaloid. Of 18S patients with cholera, those given tetracycline or tetracycline + berberine had considerably reduced volume and frequency of diarrheal stools, duration of diarrhea, and volumes of required intravenous and oral rehydration fluid. Berberine did not produce an antisecretory effect, but analysis by factorial design equations showed a reduction in diarrheal stools by one liter and a reduction in cyclic AMP concentrations in stools by 77% in the groups given berberine. Many fewer patients given tetracycline or tetracycline + berberine excreted vibrios in their stools after 24 hours in comparison with those given berberine alone. Neither tetracycline nor berberine had any benefit over placebo in 215 patients with noncholera diarrhea [219]. 

VI. The Mechanism by Which Glycoprotein Hormones, Interferon, and the Bacterial Toxins Effect Cell Changes - Current views regarding the mechanism of action of TSH and other glycoprotein hormones invoke alterations in the concentration of cyclic AMP as the second event in the transfer of information from the hormones to the appropriate cell.1 That is, the information carried by the hormone is purportedly translated into a "second message" by means of a change in intracellular cyclic AMP concentration. 

Wurster, B. R. Mohn. 1987. Spike-shaped oscillations in the absence of measurable changes in cyclic AMP concentration in a mutant of Dictyostelium discoideum. J. Cell Science 87 723-30. 

Garbers DL. 1981. The elevation of cyclic AMP concentrations in flagella-less sea urchin sperm heads. / Biol Chem 256 620-624. 

Leppla SH. Anthrax toxin edema factor A bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells. Proc Natl Acad Sci USA 1982 79(10) 3162-3166. 

The second class of small molecules exhibiting a regulating effect on enzyme yield are those associated with catabolite repression, of which cyclic AMP is a prime example (see Section 111). Cyclic AMP is usually added to the cell-free system, as its omission results in greatly diminished enzyme activity [24,25], A typical curve showing the dependence of galactosidase activity on cyclic AMP concentration is presented in Fig. 6. Synthesis of transacetylase activity, the product of the third structural gene of the lac operon, is also strongly dependent on the presence of... 

Basal cyclic AMP concentration in liver was 3.97 jumole/gprot., which increased suddenly and reached its first peak of 7.90 at 1 hour after hepatectomy. After decreasing transiently at 6 hours, it again increased and reached its second peak of 7.87 at 12 hours. 

Rats were killed by decapitation and samples of blood were collected for glucose determination and fatty acid composition. Samples of liver were taken to measure cyclic AMP concentration. 

Fig. 5. Time course of the effect of 10 fjg LH/5 ml on cyclic AMP accumulation and steroidogenesis. The changes in cyclic AMP concentration are shown as broken lines and the rates of steroidogenesis by solid lines. The control values are shown as open circles and the values obtained from LH treated tissue as solid circles. The incubation conditions were the same as in Fi. 4 except that the cyclic AMP and steroid determinations were made at various times during the second incubation.

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