Prostaglandin adenylate cyclase activation

Li+ also inhibits several hormone-stimulated adenylate cyclases which, in some cases, appear to be related to side effects of Li+ therapy. For instance, Li+ inhibits the hydro-osmotic action of vasopressin, the antidiuretic hormone which increases water resorption in the kidney [136]. This effect is associated with polyuria, a relatively harmless side effect sometimes experienced with Li+ treatment, which arises from the inability of the kidney to concentrate urine. Li+ has been shown to inhibit vasopressin-stimulated adenylate cyclase activity in renal epithelial cells. Additionally, Li+ is reported to enhance the vasopressin-induced synthesis of prostaglandin E2 (PGE2) in vitro in kidney. PGE2 inhibits adenylate cyclase activity by stimulation of Gj, and, therefore, this effect may contribute to the Li+-induced polyuria. 

Misoprostol is a stable analog of prostaglandin Ei. It reduces acid secretion by inhibiting histamine-stimulated adenyl cyclase activity in the parietal cell. 

Hillard CJ, Bloom AS (1983) Possible role of prostaglandins in the effects of the cannabinoids on adenylate cyclase activity. Eur J Pharmacol 91 21-27... 

Some hormones inhibit adenylate cyclase activity. Such molecules depress cellular protein phosphorylation reactions because their receptors interact with G, protein. When Gi is activated, its ( subunit dissociates from the /fydimer and prevents the activation of adenylate cyclase. For example, because its receptors in adipocytes are associated with G PGK, (prostaglandin H,) depresses lipolysis. (Recall that lipolysis is stimulated by glucagon and epinephrine.)... 

Aktories, K., Schultz, G., and Jakobs, K.H., 1980. Regulation of adenylate cyclase activity in hamster adipocytes. Inhibition by prostaglandins, alpha-adrenergic agonists and nicotinic acid. Naunyn-Schmiedeberg s Archives of Pharmacology. 312 167-173. 

Two major second messenger systems have been evolved. When the a-sub-unit is temporarily linked to adenylate cyclase, the enzyme is activated and catalyzes the transformation of ATP to cAMP. This second messenger activates a specific protein kinase, which in turn phosphorylates target proteins in the cell leading to the overall physiological response. Such a pathway is utilized by the /1-adrenoceptor, dopaminergic, and prostaglandin receptors, etc. 

A notable finding was the defective transport of D-glucose, uridine, and two amino acid analogs (2-aminobutanoate and cycloleucine) in chick-embryo cells in which glycosylation of proteins was prevented by tunicamycin. Other membrane-associated processes, such as the enzymic activities of Na/K ATPase and adenylate cyclase, or the stimulation of adenylate cyclase by a prostaglandin and cholerae toxin, were not affected.546... 

In recent work on CHO cells, it had been suggested that the effects of butyrate are mediated by cyclic AMP (18). We found, however, that cyclic AMP (2 mM), its mono- (1 mM and dibutyryl (0.5 mM) derivatives, theophylline and prostaglandins did not cause an elevation in si alyl transferase activity (1). Choleragen, which is a potent and persistant activator of adenylate cyclase (see below), also did not elevate sialyl transferase activity in HeLa cells (Table I) or alter cell morphology (unpublished observations). Thus, it is unlikely that these effects of butyrate are mediated by elevation of cyclic AMP levels. 

Rather than being reincorporated into inositol phospholipids, DAG can be broken down to release some arachidonate which is the precursor of prostaglandin E which, in turn, can react with plasma membrane receptors linked to adenyl cyclase and cAMP production. IL-3 does not activate phospholipase C but does promote phosphorylation of the glucose transporter by phosphokinase C (Dexter and Spooner, 1987). 

All of these three 7-thia-prostanoids show interesting biological activities. 7-Thia-13-prostynoic acid 14 is an inhibitor of the contraction of the gerbil colon, and of the stimulation of adenylate cyclase in the mouse ovary caused by prostaglandin Ej. This inhibition is as effective as for the 7-oxa-analog. Compound 14... 

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