Cyclic AMP synthesis

H2 receptors are intronless GPCRs linked to G, proteins and cyclic AMP synthesis 256... 

Since Nirenberg and his collaborators (5,6,11) have reported that in NG108-15 cells, opiates produce an initial inhibition of cyclic AMP synthesis (0 to 30 min), followed by a period in which the cell adjusts and cyclic AMP levels return to normal (lO -30 hrs), and finally a period where cyclic AMP levels are elevated (when the drug is removed or metabolized supposed withdrawal) it was of interest to follow the time-course of the inhibition. 

Catabolite repression is a two-part system. The first component is the small-molecule regulator, cyclic AMP. Glucose decreases cyclic AMP synthesis. The second component is cyclic AMP binding protein, CAP. CAP binds cAMP and thereby helps RNA polymerase bind to the promoter. When bound to cAMP, CAP binds to a sequence at the 5 end of the lac promoter. CAP binding bends the DNA, allowing protein-protein contact between CAP and polymerase. It therefore behaves in the opposite manner of repressor. Repressor (LacI) binds to operator DNA only in the absence of its small-molecule ligand, while CAP binds to promoter DNA in the presence of its small-molecule ligand. 

Y. Yamagata, H. Inoue and K. Inomata (1995). Specific effect of magnesium ion on 2, 3 -cyclic AMP synthesis from adenosine and trimetaphosphate in aqueous solution. Origin Life Evol. Biosph., 25, 47-52. 

In plasma membrane preparations, binding of ACTH to its receptor activates adenylate cyclase. In common with other receptors which activate adenylate cyclase, the interaction of ACTH with adenylate cyclase appears to require the action of a G-protein, presumably Gs, since ACTH stimulation of cyclic AMP synthesis in plasma membrane preparations is enhanced by GTP, by non-hydrolysable GTP... 

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. 

The 5-ITT and 5-HTj receptors also couple to G -adenylyl cyclase their affinity for clozapine may relate to its antipsychotic efficacy (see Chapters 11 and 18). Of the two subtypes of 5-HT receptors, the 5-HT receptor seems to inhibit cyclic AMP synthesis, while 5-HT receptor-effector coupling has not been described. 

Paralleling membrane studies, forskolln elicits Increases In Intracellular cyclic AMP In the eye- mutants of the S49 lymphoma cell line which are about ten-fold less than the Increase elicited in wild type S49 lymphoma cellsSimilar results are seen in the H21a mutant which contains a lesion In Ns impairing Its coupling to the catalytic subunit. A maximal stimulation of cyclic AMP synthesis by forskolln in S49 cells requires the presence of a functional Ns protein. 

Forskolln stimulation of cyclic AMP synthesis in C6-2B rat astrocytoma cells is decreased after the cells are grown In the presence of cyclohexlmide, a protein synthesis inhibitor. 0 This occurs without the loss of isoproterenol or cholera toxin stimulated adenylate cyclase. It was suggested that the cyclohexlmide blocks the synthesis of a protein which has a high turnover rate and is required for forskolln stimulation of adenylate cyclase. 

In another direction one must consider that adenosine accumulation could lead to other biochemical effects. It has been known for some time that adenosine can stimulate cyclic AMP synthesis in brain slices... 

For the sake of simplicity we shall assume that the era/site is a highly specialized promoter site, that is, the site for RNA polymerase attachment, and initiation of mRNA synthesis, the activator functional site, and that it includes the binding site for the cyclic AMP-activated CAP. AraO is the site on the DNA for repressor attachment. The efficiency of transcription of the operon is therefore dependent upon the concentration of (1) cyclic AMP (which is controlled by accumulated intermediates in L-arabinose metabolism through their effect on cyclic AMP synthesis... 

The role that cyclic nucleotides may play in the etiology and/or maintenance of a number of disease states is becoming clearer. In asthma, the ability of patients with this disease to excrete increased amounts of cyclic AMP in urine in response to epinephrine is greatly diminished, possibly due to a disease-related decrease in the sensitivity of adenylyl cyclase (AC) to the catecholamine. This lack of AC sensitivity however could be reversed by corticoid therapy in accord with the long established permissive effects of these hormones on cyclic AMP synthesis. In nephrogenic diabetes insipidus, diminished urinary production of cyclic AMP in response to ADH was also reported. Other conditions that may involve deficient cyclic AMP production include hypertension , psoriasis and stroke . On the other hand, cyclic AMP production appears... 

Figure 4. Cyclic AMP synthesis and degradation. Abbreviations used are ATP, adenosine triphosphate A.C., adenylate cyclase, P.D.E., phosphodiesterase 5 -AMP, 5 -adenosine monophosphate.

Earner, J., 1990. Insulin and the stimulation of glycogen synthesis The road from glycogen structure to glycogen synthase to cyclic AMP-dependent protein kinase to insulin mediators. Advances in Enzymology 63 173-231. 

When AMP is heated under reflux in DMF, the 2, 3 -cyclic phosphate is formed, and cyclic phosphates can also be obtained from nucleosides and ortho-, pyro-, or poly-phosphoric acids under the same conditions. Promotion of phosphorylation by DMF is well known and the reaction with AMP is probably intermolecular as no 3, 5 -cyclic AMP can be detected. Minor products in the latter reaction are the 2, 3 -cyclic 5 -diphosphate and the 2 (30,5 -diphosphate. The synthesis of adenosine 2 (3 )-phosphate 5 -pyrophosphate has been achieved by the phosphoromorpholidate method used in a synthesis of Co A. ... 

Wakil. Fatty acid synthesis dependent on HC03 Chance. Double-beam spectophotometer introduced. Sutherland. Discovery of cyclic AMP. Skou identified the sodium pump as a Na+/K+ dependent ATPase in the cell membrane. 

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... 

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