Monophosphates, cyclic

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. 

Adenylyl Cyclases Guanylyl Cyclases Transmembrane Signalling Cyclic Adenosine Monophosphate Cyclic Guanosine Monophosphate Cyclic Nucleotide-gated Channels Phosphodiesterases... 

Cyclic-AMP Response Element Binding Protein Cyclic GMP-dependent Protein Kinase Cyclic GMP-regulated Phosphodiesterases Cyclic Guanosine Monophosphate (Cyclic GMP cGMP)... 

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. 

Acetylcholine works with other neurotransmitters (i.e., cyclic guanylate monophosphate, cyclic adenosine monophosphate, vasoactive intestinal polypeptide) to produce penile arterial vasodilation and ultimately an erection. 

Guanylate cyclase converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cyclic GMP). 

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). 

The mechanism of the action of nitrates is not completely known, though it is reasonably likely that within smooth muscle cells, nitrates are transformed into nitrites, which then release NO. This, in turn, reacts with guanylatecyclase, causing increased synthesis of guanosine 3, 5 -monophosphate (cyclic GMP). As a result, a GMP-requiring protein kinase is activated, which results in less phosphorylation of muscle protein. Dephosphorylated muscle proteins are less able to contract, which ultimately results in a reduction of the heart s need for oxygen. 

It has been suggested139 that adenosine 3 5 -monophosphate (cyclic AMP) functions as an intracellular second messenger which mediates the effects of specific hormones on their target cells. According to this concept, a hormone such as... 

Guanylyl cyclases (Fig. 12-10) are another type of receptor enzyme. When activated, a guanylyl cyclase produces guanosine 3, 5 -cyclic monophosphate (cyclic GMP, cGMP) from GTP ... 

Dipyridamole (Persantine) is a vasodilator that, in combination with warfarin, inhibits embolization from prosthetic heart valves and, in combination with aspirin, reduces thrombosis in patients with thrombotic diseases. Dipyridamole by itself has little or no benefit in fact, in trials where a regimen of dipyridamole plus aspirin was compared with aspirin alone, dipyridamole provided no additional beneficial effect. Dipyridamole interferes with platelet function by increasing the cellular concentration of adenosine 3, 5 -monophosphate (cyclic AMP). This effect is mediated by inhibition of cyclic nucleotide phosphodiesterase and by blockade of uptake of adenosine, which acts at A2 receptors for adenosine to stimulate platelet adenylyl cyclase. The only current recommended use of dipyridamole is for primary prophylaxis of thromboemboli in patients with prosthetic heart valves the drug is given in combination with warfarin. 

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)... 

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