Adenosine monophosphate cyclic AMP

Cyclic adenosine monophosphate (cyclic AMP), a modulator of hormone action, is related to AMP (Problem 29.24) but has its phosphate group linked to two hydroxyl groups at C3 and C5 of the sugar. Draw the structure of cyclic AMP. 

The properties of a particular molecule are due to the types and number of atoms it contains and how those atoms are arranged in space. Caffeine is a stimulant because it has the same shape as one part of cyclic adenosine monophosphate (cyclic AMP), a molecule that helps to regulate the supply of energy in the brain. When caffeine is absorbed into the blood and carried to the brain, it binds to an enzyme that normally controls the supply of cyclic AMP. As a result, the enzyme can no longer bind cyclic AMP, the brain s supply of this energy-regulating molecule is increased, and we feel stimulated. 

For example, the stimulation of )6-adrenoceptors by noradrenaline results in the activation of adenylate cyclase on the irmer side of the nerve membrane. This enz)nne catalyses the breakdown of ATP to the very labile, high-energy compound cyclic 3,5-adenosine monophosphate (cyclic AMP). Cyclic AMP then activates a protein kinase which, by phosphorylating specific membrane proteins, opens an ion charmel to cause an efflux of potassium and an influx of sodium ions. Such receptors are termed metabotropic receptors. 

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). 

Some, but not all, of the pharmacological effects of eicosanoids are mediated through alterations in the concentration of cyclic adenosine monophosphate (cyclic AMP). For example, prostaglandins Ej and E2 inhibit platelet aggregation by increasing the cyclic AMP concentration. Conversely,... 

Histamine stimulation of parietal cell function by increasing the formation of cyclic adenosine monophosphate (cyclic AMP)... 

In 1963 he became professor of physiology at Vanderbilt University in Nashville, Tennessee. He was awarded the Nobel Prize for physiology or medicine in 1971 for isolation of cyclic adenosine monophosphate (cyclic AMP) and for demonstrating its involvement in numerous animal metabolic processes. From 1973 until his death he was a member of the faculty of the University of Miami Medical School. 

Adenylyl-cyclase/cAMP system. Sutherland s studies revealed that the intracellular messenger cyclic 3, 5 -adenosine monophosphate (cyclic-AMP) is a nucleotide synthesized within the cell from ATP by the action of adenylyl-cyclase. Receptors linked to Gs activate adenylyl-... 

Chemical mediators include histamines (proteins that are potent vasodilators), cytokines (small proteins that mediate and regulate the immune system, inflammatory response and hematopoiesis [red cell production]), serotonin (CNS neurotransmitter), ECF-A (eosinophil chemotatic factor of anaphylaxis) and leukotrines. Histamine and ECF-A are strong bronchoconstrictors that stimulate the contraction of bronchial smooth muscles. Cyclic adenosine monophosphate (cyclic AMP or cAMP) maintains bronchodilation. Histamines, ECF-A, and... 

The pharmacologic effects of beta-adrenergic agonist drugs, including albuterol, are at least in part attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3, 5 -adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. 

TRH is synthesized in a wide area of the hypothalamus and is controlled by a non-ribosomal enzyme,TRH-synthetase [31]. It is stored in the median eminence and secreted when required into the hypophysial portal vessels [32]. TRH binds to membrane receptors on the pituitary cells [33] and increases both the synthesis [34] and the release [35] of TSH. Since TRH has been shown to activate adenyl cyclase [36], this action is believed to be mediated via 3, 5 -cyclic adenosine monophosphate (cyclic AMP). The half-life of TRH in vivo is approximately 4 min. It is destroyed in the blood by enzymatic (TRH-degrading enzyme) cleavage of the amide group [37] and excreted via the kidney [32]. The TRH-degrading enzyme is present both in peripheral and hypophysial portal blood of rats but TRH is more rapidly destroyed in the peripheral blood. On the basis of these results, it has been suggested that the portal blood either contains only a low concentration of enzyme or that it contains high concentrations of unidentified substances which act as competitive inhibitors of or substrates for the enzyme [38]. 

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