Adenosine formation intracellular adenosin

Lloyd, H. G., Lindstrom, K. Fredholm, B. B. (1993). Intracellular formation and release of adenosine from rat hippocampal slices evoked by electrical stimulation or energy depletion. Neurochem. Int. 23 (2), 173-85. 

To date, five subtypes of these receptors have been cloned. However, initial studies relied on the pharmacological effects of the muscarinic antagonist pirenzepine which was shown to block the effect of several muscarinic agonists. These receptors were termed Mi receptors to distinguish them from those receptors for which pirenzepine had only a low affinity and therefore failed to block the pharmacological response. These were termed M2 receptors. More recently, M3, M4 and M5 receptors have been identified which, like the Mi and M2 receptors occur in the brain. Recent studies have shown that Mi and M3 are located posts)maptically in the brain whereas the M2 and M4 receptors occur pres)maptically where they act as inhibitory autoreceptors that inhibit the release of acetylcholine. The M2 and M4 receptors are coupled to the inhibitory Gi protein which reduces the formation of cyclic adenosine monophosphate (cyclic AMP) within the neuron. By contrast, the Mi, M3 and M5 receptors are coupled to the stimulatory Gs protein which stimulates the intracellular hydrolysis of the phosphoinositide messenger within the neuron (see Figure 2.8). 

The Ga proteins can be classified on the basis of similarities in their amino acid sequences and coupling to effector proteins. The four major categories are Gas, Gai, Gaq, and Gall and these are responsible for activating different signaling pathways in cells. Gas and Gai stimulate and inhibit adenylate cyclase, respectively. Adenylate cyclase is an enzyme that catalyzes the formation of cyclic adenosine monophosphate (cAMP), an intracellular second messenger... 

Adenylate cyclase is considered as a second messenger that catalyzes the formation of cAMP (cyclic adenosine monophosphate) from ATP this results in alterations in intracellular cAMP levels that change the activity of certain enzymes—that is, enzymes that ultimately mediate many of the changes caused by the neurotransmitter. For example, there are protein kinases in the brain whose activity is dependent upon these cyclic nucleotides the presence or absence of cAMP alters the rate at which these kinases phosphorylate other proteins (using ATP as substrate). The phosphorylated products of these protein kinases are enzymes whose activity to effect certain reactions is thereby altered. One example of a reaction that is altered is the transport of cations (e.g., Na+, K+) by the enzyme adenosine triphosphatase (ATPase). 

Brattleboro homozygotes) had intact arginine vasopressin-dependent cyclic adenosine monophosphate generation. The activity of cyclic adenosine monophosphate phosphodiesterase was not affected in lithium-treated rats. Hence, it seems that the main cellular effect of lithium involves impairment of arginine vasopressin-sensitive adenylate cyclase and that this results in impairment of intracellular cyclic adenosine monophosphate formation. 

Approximately 80% of red blood cell purines are in the form of adenosine triphosphate (ATP) with an intracellular concentration estimated to be 2-3 mM. In glucose-deprived or aged red cells there is a progressive decline in the ATP content of the erythrocyte leading to the formation of adenosine diphosphate (ADP) and adenosine monophosphate (AMP) AMP is then dephosphorylated (via 5 -nucleotidase) to... 

Activation of the LH receptor results in an increase of intracellular cyclic adenosine monophosphate (cAMP) levels via activation of a G protein and adenylate cyclase. In the presence of elevated concentrations of cAMP, cholesterol esterase activation occurs. This enzyme catalyzes the cleavage of cholesterol esters to free cholesterol, v/hich is then converted in mitochondria to pregnenolone as described previously. The formation of progesterone from pregnenolone is catalyzed by 5-ene-3p-hydroxysteroid dehydrogenase and 3-oxosteroid-4,5-isomerase (steps c and d in Fig. 46.3). 

Under normal conditions, induction and catabolite repression together insure that inducible enzymes are only produced in the presence of substrate but that when several substrates are present, only the enzymes acting on the best substrate are formed. Very recent studies implicate inhibition of cyclic 3, 5 -adenosine monophosphate formation as the key factor in catabolite repression (Perlman and Pastan, 1969). Cyclic 3, 5 -adenosine monophosphate reverses catabolite repression of many enzymes in E. coli and its intracellular concentration is depressed 1000-fold by growth on glucose. 

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