Intracellular cyclic AMP

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]. 

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. 

Abrams DB, Monti PM, Carey KB, Pinto RP, Jacobus SI (1988) Reactivity to smoking cues and relapse two studies of discriminant validity. Behav Res Ther 26(3) 225-233 American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn (DSM-IV). American Psychiatric Association, Washington, DC Asghari V, Sanyal S, Buchwaldt S, Paterson A, Jovanovic V, Van Tol HH (1995) Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J Neurochem 65(3) 1157-1165... 

Cyclic AMP (adenosine 3, 5 -cyclic monophosphate) is anotter secondary messenger that acts as an intracellular mediator for many different hormones, communicating the signal through the cyclic AMP-dependent protein kinase. This, in turn, phosphorylates other proteins at ine and threonine residues. Certain cell-surfece receptors act by increasing the concentration of intracellular cyclic AMP. A long-duration sudden increase of intracellular cyclic AMP takes place with cholera toxins in intestinal epithelial cells. Other cell-surfece receptors play the opposite role of decreasing the concentration of cyclic AMP. 

Among the methylxanthines, aminophylline is most commonly used drug in the treatment of bronchial asthma. It is a stable mixture of theophylline and ethylenediamine. These drugs inhibit the enzyme phosphodiesterase, this inhibition results in higher concentration of intracellular cyclic AMP. 

Several mechanisms have been proposed for the actions of methylxanthines, but none has been firmly established. At high concentrations, they can be shown in vitro to inhibit several members of the phosphodiesterase (PDE) enzyme family (Figure 20-3). Because the phosphodiesterases hydrolyze cyclic nucleotides, this inhibition results in higher concentrations of intracellular cyclic AMP (cAMP) and, in some tissues, cGMP. CAMP is responsible for a myriad of cellular functions including, but not limited to, stimulation of cardiac function, relaxation of smooth muscle, and reduction in the immune and inflammatory activity of specific cells. 

Poli, E., C. Pozzoli, C., Coruzzi, G., Bertaccini, G., 1993. Histamine H3 receptor-mediated inhibition of duodenal cholinergic transmission is independent of intracellular cyclic AMP and GMP. Gen. Pharmacol. 24, 1273-1278. 

FIGURE 26-1 Mechanism of action of beta agonists on respiratory smooth muscle. Beta agonists facilitate bronchodilation by stimulating adenyl cyclase activity, which in turn increases intracellular cyclic AMP production. Cyclic AMP activates protein kinase, which appears to add an inhibitory phosphate group to contractile proteins, thus causing muscle relaxation and bronchodilation. 

The nature of the second messenger(s) involved in the action of prolactin on Nb2 cells has been studied [108]. Levels of intracellular cyclic AMP do not change when the cells are treated with prolactin, and cyclic AMP analogues and phosphodiesterase inhibitors do not induce proliferation. Similarly, no clear evidence could be obtained for a clear-cut involvement of prostaglandins in Nb2 cell proliferation. 

Asghari V, Sanyal S, Buchwaldt S, Paterson A, Jovanovic V, Van Tol HH (1995) Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J Neurochem 65 1157-1165. 

Hoover, D.L., Friedlander, A.M., Rogers, L.C., Yoon, I.K., Warren, R.L., Cross, A.S. (1994). Anthrax edema toxin differentially regulates lipopolysaccharide-induced monocyte production of tumor necrosis factor a and interleukin-6 by increasing intracellular cyclic AMP. Infect. Immun. 62 4432-9. 

The binding of histamine to its Hj-receptor on the parietal cell causes activation of the membrane-bound adenylate cyclase with a corresponding increase in intracellular cyclic AMP levels. The binding of acetylcholine or gastrin to their specific receptors increases intracellular calcium. Increased... 

P-adrenergic blockade. There is increased tissue sensitivity to catecholamines in h) erth5Toidism with an increase in either the number of 3-adrenoceptors or the second messenger response (i.e. intracellular cyclic AMP synthesis) to their stimulation. Therefore some of the xmpleasant symptoms are adrenergic. 

Saltzman LE, Moss J, Berg RA, Horn B, Crystal RG. 1982. Modulation of collagen production by fibroblasts effects of chronic exposure to agonists that increase intracellular cyclic AMP. Biochem. J. 204 25-30... 

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. 

FIGURE 14.9 (A) Intracellular cyclic AMP levels in cells transfected with high levels of P-adrenoceptor. It can be seen that the... 

Dopamine receptors (Dj and D2) have a greater affinity for DA than for NE or E (Table 32-3). Both subtypes exert effects by altering the activity of adenylate cyclase via a G-protein. Di receptors coupled to Gsa activate the enzyme and cause a rise in intracellular cyclic AMP. D2 receptors are coupled to G i, and inhibit the enzyme (Table 32-3). At very high concentrations, however, dopamine is capable of activating a-adrenergic receptors, which results in an effect resembling that of NE (vasoconstriction) instead of the characteristic vasodilatation elicited by low concentrations of DA. 

Regulation of cellular activities by cyclic AMP-dependent protein kinase (PKA) is a critical pathway in neuronal responses via the potassium channel A-current (Childers and Deadwyler 1996). In rat hippocampal cells, PKA phosphorylation of the potassium channel produced a negative shift in the voltage-dependence (Deadwyler et al. 1995). CBi receptor stimulation resulted in a decrease in intracellular cyclic AMP, net dephosphorylation of the channels, activation of the A-type potassium currents, and hyperpolarization of the membrane (Deadwyler et al. 1995 Hampson et al. 1995). The significance of cannabinoid-mediated hyperpolarization of the axon terminals is that it can cause a depression in the response to depolarizing stimuli and failure in neurotransmitter release at the synapse (Childers and Deadwyler 1996). 

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