CAMP cyclic adenosine monophosphate action

FIGURE 52.5 The actions of glipizide. ATP = adenosine triphosphate ADP = adenosine diphosphate cAMP = cyclic adenosine monophosphate. 

Mechanisms of action of dipyridamole. Abbreviations ADR adenosine diphosphate AMP, adenosine monophosphate cAMP, cyclic adenosine monophosphate cGMR guanosine cyclic monophosphate NO, nitric oxide. 

Mechanisms of action of cilostazol. Abbreviations cAMP, cyclic adenosine monophosphate cGMP, guanosine cyclic monophosphate HGF, hepatocyte growth factor MCP-I, monocyte chemoattractant protein-1 NO, nitric oxide. 

Fig. 3. Summary of key mechanisms of action through which a model adrenotoxicant (indicated by a black star) could disrupt the synthesis of corticosteroids. References presenting data in support of this model are given in the text. ACTH, adrenocorticotropic hormone Rc, receptor G, G-protein AC, adenylyl cyclase Ca, calcium ATP, adenosine triphosphate cAMP, cyclic adenosine monophosphate PKA, protein kinase A StAR, Steroid acute regulatory protein SCC, P450SCO, cholesterol side chain cleaving enzyme 11/3, 11/3-hydroxylase 17a, 17a-hydroxylase 3/3-HSD, 3/3-hydroxysteroid-5A-steroid dehydrogenase C21, 21-hydroxylase ER, endoplasmic reticulum.

Factors controlling calcium homeostasis are calcitonin, parathyroid hormone(PTH), and a vitamin D metabolite. Calcitonin, a polypeptide of 32 amino acid residues, mol wt - SGOO, is synthesized by the thyroid gland. Release is stimulated by small increases in blood Ca " concentration. The sites of action of calcitonin are the bones and kidneys. Calcitonin increases bone calcification, thereby inhibiting resorption. In the kidney, it inhibits Ca " reabsorption and increases Ca " excretion in urine. Calcitonin operates via a cyclic adenosine monophosphate (cAMP) mechanism. 

The nucleotide cyclic AMP (3, 5 -cyclic adenosine monophosphate, cAMP) is a cyclic phosphate ester of particular biochemical significance. It is formed from the triester ATP by the action of the enzyme adenylate cyclase, via nucleophilic attack of the ribose 3 -hydroxyl onto the nearest P=0 group, displacing diphosphate as leaving group. It is subsequently inactivated by hydrolysis to 5 -AMP through the action of a phosphodiesterase enzyme. 

Autonomic receptors further regulate calcium influx through the sarcolemma (Fig. 15.1). (3-Adrenergic stimulation results in the association of a catalytic subunit of a G protein coupled to the (3-receptor. This stimulates the enzyme adenylyl cyclase to convert ATP to cyclic adenosine monophosphate (cAMP). Increasing cAMP production results in a cAMP-dependent phosphorylation of the L-type calcium channel and a subsequent increase in the probability of the open state of the channel. This translates to an increase in transsarcolemmal calcium influx during phase 2 (the plateau phase) of the cardiac muscle action potential. The effects of transient increases in intracellular levels of cAMP are tightly con-... 

Uterine relaxation is mediated in part through inhibition of MLCK. This inhibition results from the phosphorylation of MLCK that follows the stimulation of myometrial (3-adrenoceptors relaxation involves the activity of a cyclic adenosine monophosphate (cAMP) mediated protein kinase, accumulation of Ca++ in the sarcoplasmic reticulum, and a decrease in cytoplasmic Ca. Other circulating substances that favor quiescence of uterine smooth muscle include progesterone, which increases throughout pregnancy, and possibly prostacyclin. Progesterone s action probably involves hyperpolarization of the muscle cell membrane, reduction of impulse conduction in muscle cells, and increased calcium binding to the sarcoplasmic reticulum. 

Mechanism of Action Aglucose elevating agent that promotes hepatic glycogenoly-sis, gluconeogenesis. Stimulates production of cyclic adenosine monophosphate (cAMP), which results in increased plasma glucose concentration, smooth muscle relaxation, and an inotropic myocardial effect. Therapeutic Effect Increases plasma glucose level. 

Mechanism of Action A positive inotropic agent that inhibits myocardial cyclic adenosine monophosphate (cAMP) phosphodiesterase activity and directly stimulates... 

A) Inhibition of platelet phosphodiesterases (PDEs) [91]. Quercetin and myricetin potentiated the anti-aggregatory action of prostacyclin (PGI2), a potent stimulator of platelet adenylate cyclase synthesised by the vascular endothelium, on ADP-induced platelet aggregation in washed human platelets, and the elevation of platelet cyclic adenosine monophosphate (cAMP) elicited by PGI2 [89,92,93]. These effects are probably due to an inhibition of PDEs. As suggested by Ferrell and co-workers [92], this inhibition arises from the similarity between the pyranone ring of flavonoids and the pyrimidine ring of adenine. 

A frequently cited mechanism of action for these agents is phosphodiesterase (PDE) inhibition and the associated antiplatelet effects that accompany increases in intracellular cyclic adenosine monophosphate (cAMP). In fact, the effects of these drugs go far beyond their direct effect on PDE inhibition or platelet function. This chapter discusses (/) cyclic nucleotides, PDE, and PDE inhibitors (if) the mechanisms of action of dipyridamole and cilostazol (Hi) drug issues and (iv) current clinical applications for dipyridamole and cilostazol, including recent clinical trials that may have changed our perception of the possible utility of these agents for percutaneous intervention. 

Mechanism of action The methylxanthines may act by several mechanisms, including translocation of extracellular calcium, increase in cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) caused by inhibition of phosphodiesterase, and blockade of adenosine receptors. 

Intracellular cyclic adenosine monophosphate (cAMP)-stimulated add secretion in the isolated guinea-pig gastric mucosa was not inhibited by administration of an H2-receptor antagonist, as expected, although H 83/69 (timoprazole) induced a dose-dependent inhibition. This was the first experimental evidence for a site of inhibitory action beyond the panel of stimulatory cell membrane receptors. Interestingly, it was found that the initial lead compound (CMN 131), had no inhibitory effect on dibutyryl-cAMP-stimulated acid secretion, nor was it an H2-receptor antagonist [9],... 

Q6 The precise mechanism of action of lithium is not known. It seems to affect (inhibit or block) mechanisms mediated by cyclic adenosine monophosphate (cAMP) and phosphatidylinositol/diacylglycerol secondary messengers. It may inhibit the release of noradrenaline and dopamine. Lithium has the ability to compete with or replace sodium ions in the body, and its excretion is related to sodium levels if sodium is depleted, lithium is retained and its toxicity increases. Lithium salts take several days (up to a week) to exert a therapeutic effect. 

The structure inhibitory activity relationships among numerous P-carboline alkaloids was studied. Harmine was found to inhibit the actions of cyclic adenosine monophosphate (cAMP) phosphodiesterase (ICS0 69.3 x 10 5 M). Among the di- and tri-substituted P-carbolines, the O-methylated P-carbolines and the O-acetylated p-carbolines had higher inhibitory activity than the corresponding hydroxy p-carbolines, while the dihydro- and tetrahydro-derivatives were not potent inhibitors [271]. 

The promotion of the synthesis of lipids (lipogenesis) and the inhibition of the release of free fatty acids (lipolysis) by insulin also requires a complex network of signalling pathways, partially coupled to those for the Glut4 activation. In adipocytes, insulin inhibits lipolysis primarily through inhibition of a hormone-sensitive lipase via reduction of the amount of cyclic adenosine monophosphate (cAMP) present in the cells. In this specific action, a phosphodiesterase is involved, ] a level where again the phosphate antagonist vanadate can interfere. 

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