Cyclic adenosine 5 -phosphate receptor

Metabotropic receptors, in contrast, create their effects by activating an intracellular G protein. The metabotropic receptors are monomers with seven transmembrane domains. The activated G protein, in turn, may activate an ion channel from an intracellular site. Alternately, G proteins work by activation or inhibition of enzymes that produce intracellular messengers. For example, activation of adenylate cyclase increases production of cyclic adenosine monophosphate (cAMP). Other effector mechanisms include activation of phospholipases, diacylglycerol, creation of inositol phosphates, and production of arachidonic acid products. Ultimately, these cascades can result in protein phosphorylation. 

Sattin A, Rail TW (1970) The effect of adenosine and adenine nucleotides on the cyclic adenosine 3 , 5 -phosphate content of guinea pig cerebral cortex slices. Mol Pharmacol 6(1) 13—23 Schulte G, Fredholm BB (2000) Human adenosine Al, A2A, A2B, and receptors expressed in Chinese hamster ovary cells all mediate the phosphorylation of extracellular-regulated kinase 1/2. Mol Pharmacol 58(3) 477-482... 

It has been long recognized that prolonged lithium therapy can cause hypothyroidism. In fact, determination of serum thyroid-stimulating hormone once a year is recommended in all subjects on prolonged lithium therapy [32, 33]. Lithium perturbs receptor-mediated signaling events such as cyclic adenosine monophosphate and inositol phosphate accumulation [34]. These effects likely explain many hormonal side effects of lithium. 

Other drugs affect intracellular calcium channels of the endoplasmic or sarcoplasmic reticulum, e.g. inositol triphosphate receptor channels open in response to InsPs itself and certain other inositol phosphates, are sensitized by thiomersal (which increases the sensitivity of the receptor to InsPs by acting as a sulphydryl reagent) and antagonized by heparin. The various ryanodine receptor channels, at which a putative natural agonist is cyclic adenosine diphosphate ribose (cADP-R), are activated by caffeine and low concentrations of ryanodine (but antagonized by high concentrations of ryanodine and ruthenium red). 

Fig. 4 Assays for G-protein-coupled receptors. The two main ciasses are binding and functional assays. Binding assays detect compounds that are ligands of the receptor. Functional assays probe the signaling of the receptor within the cell. Gs/i and Gq/i, G-proteins PLC, phospholipase C AC, adenylyl cyclase DAG, diacylglycerol cAMP, cyclic adenosine monophosphate PKC, protein kinase C PKA, protein kinase A (PKA) lns(l,4,5)P3, inositol phosphates P-CREB, phosphorylated cAMP response element binding protein CRE, cAMP regulatory element.

The muscarinic receptor is a seven-helix membrane-spanning G-protein-type receptor and the associated second messenger is either activation of inositol-3-phosphate (IPS) or inhibition of cyclic adenosine monophosphate (cAMP). There are five subtypes of the muscarinic receptors (M1-M5). All share the same general structure and the active site, but they differ in their tissue distribution, their second messenger mechanism and the associated physiological response. ... 

A significant contribution to the understanding of hormone action has been recently made by the discovery of the second messenger, adenosine-3, 5 -cyclic phosphate (cAMP) [28,29]. Many hormones, particularly the peptide ones, appear to act primarily at the cell surface where they interact with their specific receptor molecules. Such an interaction of hormone with receptor stimulates the membrane-associated enzyme, adenyl cyclase, which in turn catalyzes the production of intracellular cAMP from ATP [30,31]. Thus, this second messenger, the intracellular cAMP, becomes the mediator of hormone action, and itself regulates gene expression by as-yet-unknown mechanisms. The primary actions of many hormones are thus known, and what remains to be discovered are the actions of cAMP. 

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