Adenosine 3 : 5 monophosphate secretion, cyclic

Most pathology of cholera is thought to result from an enterotoxin that increases cyclic adenosine monophosphate-mediated secretion of chloride ion into the intestinal lumen, which results in isotonic secretion (primarily in the small intestine) exceeding the absorptive capacity of the intestinal tract (primarily the colon). 

Action on the CNS depends directly on the dose of administered drug, and can be manifested as fatigue, anxiety, tremors, and even convulsions in relatively high doses. Theophylline acts on the cardiovascular system by displaying positive ionotropic and chronotropic effects on the heart, which, can likely be linked to the elevated influx of calcium ions by modulated cyclic adenosine monophosphate and its action on specific cardiac phosphodiesterases. In the gastrointestinal system, methylxanthines simultaneously stimulate secretion of both gastric juice and digestive enzymes. 

Plasma calcium concentration is the principal factor regulating PTH synthesis and release. The increase in PTH synthesis and secretion induced by hypocalcemia is believed to be mediated through activation of parathyroid gland adenylyl cyclase and a subsequent increase in intracellular cyclic adenosine monophosphate (cAMP). 

The Hi Receptor and its Ligands. The H receptor mediates effects, through an increase in cyclic adenosine monophosphate (cAMP). such as gastric acid secretion relaxation of airway smooth muscle and of pulmonary vessels increased lower airway mucus secretion esophageal contraclion inhibition of basophil, but not mas cell histamine release inhibition of neutrophil activation and induction or suppressor T cells. There is no evidence that the H- receptor causes significant modulation of lung function in the healthy human subject or in the asthmatic. 

Maintenance of adrenal cortex Promotes secretion of steroids, oxidative phosphorylation in adrenal cortex Mobilizes and increases oxidation of free fatty acid in adipose tissue Increases gluconeogenesis in liver increases cyclic adenosine monophosphate (AMP) in adrenal cortex Decreases urea formation in liver... 

Prostaglandin inhibition of gastric acid secretion by blocking the formation of cyclic adenosine monophosphate... 

In close proximity to the parietal cells are gut endocrine cells called enterochromaffin-like (ECL) cells. ECL cells have receptors for gastrin and acetylcholine and are the major source for histamine release. Histamine binds to the H2 receptor on the parietal cell, resulting in activation of adenylyl cyclase, which increases intracellular cyclic adenosine monophosphate (cAMP). cAMP activates protein kinases that stimulate acid secretion by the H+/K+ ATPase. In humans, it is believed that the major effect of gastrin upon acid secretion is mediated indirectly through the release of histamine from ECL cells rather than through direct parietal cell stimulation. 

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],... 

Beubler E, Kollar G, Soria A, et al. (1989) Involvement of 5-hydroxytryptamine, prostaglandin E2, and cyclic adenosine monophosphate in cholera toxin-induced fluid secretion in the small intestine of rat in vivo. In Gastroenter. 96 368-376. 

A more recent cell-based in vitro assay involves the use of the microphysiometer, a sensitive extracellular pH sensor, which has been used to measure luminal (or apical) secretion and basolateral release of OH- as well as liberation of acidic metabolites in rabbit gastric glands. Adenosine 3, 5 -cyclic monophosphate stimulation produced a biphasic change... 

Cystic fibrosis is a hereditary disorder caused by mutation in the cystic fibrosis transmembrane conductance regulator gene that encodes a cyclic adenosine monophosphate-regulated chloride channel. Defects in chloride ion transport in the airway epithelia lead to abnormal airway secretions, impaired mucociliary clearance, chronic bacterial infection, bronchiectasis, and premature death. Delivery of the cystic fibrosis transmembrane conductance regulator cDNA by adenovirus vectors or the plasmid-liposome complex resulted in transient correction of the defects in patients with cystic fibrosis. Formulations of cationic lipid-DNA complexes for aerosol delivery are being explored to improve on the gene therapy approach. 

Secretory diarrhea occurs when a stimulating substance either increases secretion or decreases absorption of large amounts of water and electrolytes. Substances that cause excess secretion include vasoactive intestinal peptide (VIP) from a pancreatic tumor, unabsorbed dietary fat in steatorrhea, laxatives, hormones (such as secretin), bacterial toxins, and excessive bile salts. Many of these agents stimulate intracellular cyclic adenosine monophosphate and inhibit Na+/K+-ATPase, leading to increased secretion. Also, many of these mediators inhibit ion absorption simultaneously. Clinically, secretory diarrhea is recognized by large stool volumes (>1 L/ day) with normal ionic contents and osmolality approximately equal to plasma. Fasting does not alter the stool volume in these patients. 

Calcitonin, a polypeptide consisting of 32 amino acids, is produced by parafollicular cells (C cells) of the thyroid gland. The secretion of calcitonin is stimulated by calcium, catecholamine, and theophylline (increased cyclic adenosine monophosphate levels), glucagon, cholecystokinin, gastrin, and cerulean. 

A few observations establish the influence of bacterial components on animals, mainly protozoans. The ingestion of bacteria by protozoans may be controlled by secretions or constituent compounds of their preys. Unicellular organisms may even be able to choose the bacteria they feed on, avoiding such species as Chromobacterium or Serratia, which contain toxic or repulsive products (see Paoletti, 1964). Cyclic AMP (cyclic adenosine monophosphate), a well-known intra-cellular mediator, may play a role outside the cell, monitoring certain chemical communication systems. Chassy et al. (1969) observed that the slime mould Dictyostelum discoideum was attracted, in oligotrophic conditions, by C—AMP released by the bacteria on which it feeds. 

Biosynthesis of TRH occurs in a wide area of the hypothalamus and appears to be under the control of a nonribosomal (soluble) enzyme system, TRH synthetase (R5), which is activated by norepinephrine (G15). TRH is stored in the median eminence, from which is secreted into the hypophysial venous portal system to be transported to the anterior pituitary gland (R2). There it is specifically bound to membrane receptors (G13, W3) and activates adenyl cyclase, leading to increased production of cyclic adenosine monophosphate (K1). 

Cyclic AMP. Drugs such as the 8-adrenoceptor agonists, methylxanthines, prostaglandins and histamine Itself cause an increase in mast cell or basophil levels of cyclic adenosine 3 5 monophosphate, and this is associated with inhibition of histamine secretion Induced by an immunological stimulus (49,50,51). Whilst cyclic AMP itself does not inhibit histamine secretion Induced by an immunological stimulus, the dlbutyryl derivative which is able to pass through cell membranes is an inhibitor of secretion (52, 54), as is adenosine 3 5 cyclic phosphorothioate, which also passes into cells (53). 

Agents such as cardioactive sterols inhibit Na,K-ATPase and have positive inotropic and chronotropic effects on the heart . Adenosine-3, 5 -cyclic monophosphate (cyclic AMP) has been shown to inhibit human gastro-intestinal mucosal Na,K-ATPase responsible for gastric secretions. This observation by Mozsik may also explain the positive inotropic effects of cyclic AMP since ouabain s effects on the heart appear to be related to Na,K-ATPase inhibition. 

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]. 

Arg ]-vasopressin stimulated surfactant secretion in primary cultures of rat type 2 pneumocytes independently of adenosine 3 ,5 -cyclic monophosphate (Brown and Wood 1989). A 50% loss of tritiated phosphatidyhnsositol 4,5-biphosphate (PIP2) occurred from cells prelabeled with myo[ H]inositol within 15 s (Brown and Chen 1990). Consistent with vasopressin-induced PIP2 hydrolysis the two breakdown products, 1,2-diacylglycerol and inositol 1,4,5-triphosphate, was observed. Vasopressin stimulated protein kinase C activity twofold over the basal activity of 0.7410.07 nM/min x mg protein. The [Arg ]-vasopressin antagonist, 1-deamino-8-D-arginine vasopressin, inhibited [Arg ]-vasopressin activation of protein kinase C. 

Jeppesen PB, Gregersen S, Poulsen CR, Hermansen K (2000) Stevioside acts directly on pancreatic (3 cells to secrete insulin actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K-l—channel activity. Metabolism 49 208-214 Abudula R, Jeppesen PB, Rolfsen SED, Xiao J, Hermansen K (2004) Rebaudioside A potentially stimulates insulin secretion from isolated mouse islets studies on the dose-, glucose-, and calcium-dependency. Metabolism 53 1378-1381... 

Gaal K, Forgacs 1. Effect of cyclic adenosine monophosphate on renal function and renin secretion. Acta Physiol Acad Sci Hung 1975 46(1) 9-18. 

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