Purines adenylate cyclase

Caffeine in tea and coffee inhibits the phosphodiesterase that degrades cAMP. The resultant increase in cAMP levels, therefore, mimics the action of mediators such as the catecholamines that modulate adenylate cyclase. Caffeine and the related theophylline (both purine alkaloids, see Box 11.12) are thus effective stimulants of the CNS. 

G protein a membrane-bound protein that mediates the action of adenylate cyclase (24.3) grana bodies within tlie chloroplast that contain the thylakoid disks, the site of photosynthesis (22.1) guanine one of the purine bases found in nucleic acids (9.2)... 

Purlnerglc receptors - Receptors for the purines may be divided into P-1 and P-2 subtypes. P-1 receptors are adenosine-sensitive and cyclase-linked, while P-2 receptors are ATP-sensltlve, affect prostaglandin synthesis, and have no effect on cyclic AMP production. Two subtypes of the P-1 receptor exist he A-1 or R1 and A-2 or Ra, which, respectively, inhibit or activate adenylate cyclase. Both A-1 and A-2 receptors are sensitive to blockade by xanthines such as caffeine and theophylline. To date, ligand binding assays have only been described for the A-l and P-2 receptors. Binding studies have led to the description of further subtypes which show species... 

Incubation of A10 cells, a murine vascular smooth muscle cell line, with xanthine oxidase and purine resulted in an enhancement of adenylate cyclase activation (Tan et al. 1995). The effect of purine and xanthine oxidase was not blocked by coincubation with superoxide dismutase (which catalyses the conversion from superoxide anion to H2O2). This suggests that the generation of the superoxide anion is not involved in the mechanism of enhancement of adenylate cyclase activation. 

Studies of the effect of adenosine and its analogs on adenylate cyclase have defined two distinct adenosine sensitive sites. One extracellular site, the R site, may either activate or inhibit adenylate cyclase and this site requires the integrity of the ribose ring for activity. The other site, an intracellular site, is directly associated with the adenylate cyclase itself and has been termed the P" site. This mediates inhibition of adenylate cyclase and requires integrity of the purine ring for activity. 

In unstimulated brown adipose tissue, the mitochondria are coupled, since purine nucleotides are present in the cytosol and the proton channel is closed. When the tissue is stimulated by noradrenaline, the adenylate cyclase in the cell membrane is stimulated to produce cyclic AMP which, in turn, stimulates triglyceride breakdown and the release of fatty acids. It is believed that fatty acids at low concentration displace nucleotides from the proton channel and cause it to open, thus uncoupling the mitochondria. The tissue is then able to... 

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