Cyclic AMP and adenyl cyclase

METHODS RELATED TO CYCLIC AMP AND ADENYLATE CYCLASE-B.G. Benfey... 

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. 

The mechanism by which cheno (a di- -hydroxy-bile acid) induces diatrhea are probably related to the inhibition of water and electrolyte transport and to the activation of the adenylate cyclase cyclic AMP and guanylate cyclase cyclic GMP systems which would promote secretion of water and electrolytes. 

It appears that cyclic AMP does not mediate the action of GA (83). Two reports (85, 86) rule out the involvement of cyclic adenosine 3 ,5 -monophosphate and adenylate cyclase in the hormonal regulation of plant growth processes. Although barley aleurone cells metabolize GA s, attempts to isolate GA-binding proteins have not been successful (84). 

Fig. 9. The interaction of ACTH with the cyclic AMP and calcium intracellular messenger systems in the regulation of steroidogenesis in the adrenocortical zona glomerulosa cell comparison with angiotensin II and potassium. ACTH activates both adenylate cyclase and calcium influx, here shown as involving two receptor subtypes (R, and R2) although such receptor subtypes have not been identified. The A-kinase and calmodulin systems produce individual responses of characteristic amplitudes and time-courses, which combine to give the observed response of the intact cell. The sequence of events for ACTH is compared to those for the other two major stimuli of steroidogenesis in the zona glomerulosa cell, angiotensin II and potassium. From Ref. 41.

Adrenergic receptors belong to the G-protein coupled receptor family. The key elements are Gs, adenylate cyclase, 3, 5 -cyclic AMP and protein kinase A. 

Brooker, Gary, Newer Development in the Determination of Cyclic AMP and Other Cyclic Nucleotides, Adenylate Cyclase, and... 

Figure 6.1. Adenylate cyclase cataly.ses the formation of cyclic AMP and inorganic phosphate (centre) from ATP (left) cyclic nucleotide phosphodiesterase catalyses the formation of 5 -AMP (right) from cyclic AMP (centre)...

Protein binding can contribute to the high basal level of cyclic AMP in many tissues, and its intracellular concentration may be regulated not only by the activities of the two enzymes—adenylate cyclase (which mediates the synthesis of cyclic AMP) and phosphodiesterase (which mediates its degradation)—but also by binding proteins which protect cyclic AMP from degradation and limit its access to its sites of action. 

A useful procedure for estimating adenylate cyclase in intact cells and tissues is to incubate the tissue with labelled adenine and then measure the rate of labelling of cyclic AMP [112]. Adenine readily penetrates cells and is partially converted to ATP. In heart slices, the ATP newly synthesised from radioactive adenine was found in equilibrium with the existing pool used for the production of cyclic AMP the specific activity of the newly-formed cyclic AMP was similar in the presence and in the absence of stimulatory hormone [113]. The prelabelling method has been compared with the protein-binding method in brain slices [114,115]. Increases in total levels of cyclic AMP and increases in levels of radioactive cyclic AMP derived from intracellular adenine nucleotides labelled by prior incubation with radioactive adenine occurred on similar time courses and to similar extents. Radioactive cyclic AMP represented a small (7-13%) but relatively constant fraction of the total amount of cyclic AMP. These results provided no evidence for the presence of more than one major compartment of adenine nucleotides in brain slices that serve as a source of nucleotide precursor for cyclic AMP. The nucleotides of this compartment were uniformly labelled by incubation with radioactive adenine [116]. 

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