Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parathyroid hormone increased basal adenyl cyclase activity and that increase was inhibited by prostaglandin E(1) (PGE(1)). Tissue cyclic 3',5'-adenosine monophosphate (cyclic AMP) concentrations were increased by parathyroid hormone and that increase was likewise inhibited by PGE(1). Both parathyroid hormone and dibutyryl cyclic AMP increased (32)P incorporation into renal cortical phospholipids. PGE(1) diminished the effect of parathyroid hormone but not dibutyryl cyclic AMP to influence that parameter. PGE(1) likewise modulated the effect of parathyroid hormone but not dibutyryl cyclic AMP to decrease fractional phosphate reabsorption by the renal tubule. It is suggested that PGE(1) inhibits the effect of parathyroid hormone by decreasing its effect on adenyl cyclase. Such interaction may be important in modulating the intracellular action of parathyroid hormone on kidney cortex.
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PMID:Effect of prostaglandin E 1 on certain renal actions of parathyroid hormone. 434 30

The intravenous injection of prostaglandin E(1) (PGE(1)) causes a dose-dependent relaxation of the lower esophageal sphincter (LES) in the intact, lightly anesthetized opossum. The action of PGE(1) is not inhibited by the drugs that produce muscarinic or nicotinic cholinergic antagonism or alpha and beta adrenergic antagonism in the doses that inhibited the action of respective agonists. Moreover, this action is not affected by exogenous gastrin pentapeptide. The action of PGE(1) on the LES is mimicked by isoproterenol, theophylline ethylenediamine, and dibutyryl cyclic AMP. Both theophylline, a phosphodiesterase inhibitor, and isoproterenol, an adenyl cyclase stimulator, added to the action of PGE(1). On the other hand, adenyl cyclase inhibitor nicotinic acid, as well as phosphodiesterase stimulator, imidazole inhibited its action. Further, both nicotinic acid and imidazole inhibited the degree of LES relaxation produced by esophageal distension. These studies suggest that intracellular cyclic AMP may act as the "second messenger" in the regulation of the lower esophageal sphincter relaxation.
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PMID:Mechanism of the lower esophageal sphincter relaxation. Action of prostaglandin E 1 and theophylline. 434 7

Both cholera enterotoxin and certain prostaglandins have been shown to stimulate intestinal fluid secretion in vivo, to cause ion flux changes in vitro similar to those caused by addition of cyclic 3',5'-adenosine monophosphate (cyclic AMP), and to activate intestinal mucosal adenyl cyclase. It has been suggested that the effects of the enterotoxin on intestinal cyclic AMP metabolism may be indirect, and that locally synthesized prostaglandins may serve as required intermediates for the effects of the enterotoxin in activating intestinal mucosal adenyl cyclase. In order to clarify certain aspects of the mechanisms by which these two agents alter intestinal mucosal cyclic AMP metabolism and ion transport, their effects on cyclic AMP accumulation in rabbit ileal mucosa were examined in vitro. Addition of 5 mug per ml (75 mug per 150 mg mucosa) of purified cholera enterotoxin produced a peak increase in cyclic AMP level in 3 h but there was a time delay of at least 30 min before any effect was observed. Inhibition of cyclic nucleotide phosphodiesterase with theophylline failed to reduce this time delay. In contrast, addition of prostaglandin E(1) (PGE(1)) increased the cyclic AMP level rapidly, a peak effect being observed in 2 min. The time of the peak prostaglandin-induced changes in cyclic AMP level and short-circuit current correlated closely. A maximal increment in cyclic AMP level was achieved with 5 x 10(-5) M PGE(1). When 10(-4) M PGE(1) was added to mucosa already maximally stimulated with cholera toxin, the resulting cyclic AMP level was equal to the sum of the levels reached when each agent was added alone. Furthermore, the effects of the enterotoxin on mucosal cyclic AMP levels were not influenced by indomethacin under conditions where mucosal prostaglandins synthesis was inhibited. The results suggest that endogenous prostaglandins do not provide an essential link in the activation of intestinal mucosal adenyl cyclase by cholera enterotoxin. The present study also indicates that the effect of cholera enterotoxin on intestinal mucosal cyclic AMP metabolism involves a definite time delay which is not due to cyclic nucleotide phosphodiesterase activity.
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PMID:Effects of prostaglandins and cholera enterotoxin on intestinal mucosal cyclic AMP accumulation. Evidence against an essential role for prostaglandins in the action of toxin. 435 41

We have shown that two unrelated prostaglandin antagonists block both thyrotropin (TSH) and prostaglandins E (PGE(1), PGE(2)) stimulation of thyroidal adenyl cyclase activation and cyclic 3',5'-adenosine monophosphate (cAMP) formation, suggesting that prostaglandins play an important role in regulating thyroid function. To further explore this postulate, we measured prostaglandin content by radioimmunoassay in homogeneous bovine thyroid cell preparations in the presence and absence of TSH. Antibodies to albumin-conjugated PGE(1) and PGF(2alpha) showed specificity for prostaglandins E and F, respectively, but reacted, albeit far less effectively, with heterologous prostaglandins. A double antibody system was used to separate free from antibody-bound PGE(1)-(3)H and PGF(2alpha)-(3)H. Thyroid cells were extracted with ethanol/ethyl acetate and the various prostaglandins separated on silicic acid columns. Recoveries of added PGE(1)-(3)H and PGF(2alpha)-(3)H through the extraction and separation procedures ranged from 50-80%. The sensitivity of the method was 10-50 pg. Basal thyroid cell content of PGE(1) and PGF(2alpha) "equivalents" varied between cell preparations (range = 2-6 ng/0.2 ml cell suspension) but, in each instance, remained constant during 5-30-min incubations at 37 degrees C. TSH, 10-100 mU/ml, increased the levels of cell PGE(1) and PGF(2alpha) "equivalents" 30-80% above basal during 5-15-min incubations. The stimulatory effect was specific for TSH, no increase in PGE(1) or PGF(2alpha) "equivalent" levels being seen with luteinizing hormone (LH), human growth hormone (HGH), adrenocorticotropic hormone (ACTH), or glucagon. These data support the thesis that prostaglandins may mediate TSH effects on thyroid.
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PMID:Thyrotropin increases prostaglandin levels in isolated thyroid cells. 462 70

Somatomedin in concentrations between 3 and 20 units per milliliter significantly inhibits the basal activity of adenylate cyclase in crude membrane preparations obtained from homogenates of fat cells, liver, and spleen lymphocytes of the rat, and from chondrocytes and cartilage of chick embryos. The enzyme activity measured in the presence of stimulating hormones (epinephrine, prostaglandin PGE(1), parathyroid hormone) is also inhibited in these preparations by somatomedin. These observations may be relevant in a general way to the mechanism of action of growth-prmoting substances and to the processes which normally regulate cell growth.
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PMID:Somatomedin: inhibiton of adenylate cyclase activity in subcellular membranes of various tissues. 470 May 95

Research on the physiopathologic and biochemical nature of prostaglandins (PGs) suggest that PGs play a role in reproductive physiology. In vitro studies show that the PGE series decrease the motility of the human uterus, fallopian tubes, and ureter, and produce vasodilatation. PGFs cause vasoconstriction and increased motility of the uterus, fallopian tubes, ureter, and gastrointestinal muscle. PGs are also known to inhibit lipolysis, platelet aggregation, and gastric secretion. The exact mechanism of PGs are not fully understood, but evidence suggests that many responses can be attributed to interference with the enzyme adenyl cyclase, which catalyzes the formation of adenosine 3',5'-monophosphate (cyclic AMP) from adenosine triphosphate. The adenyl cyclase-cyclic AMP system mediates lipolysis, steroidogenesis, gastric secretion, certain smooth muscle motility responses, and increase in permeability due to vasopressin. Early studies of the myometrial effects of PGs showed that the PGE series inhibited the motility of the human myometrium in vitro while the PGF series produced mixed responses. The role of PGF2alpha in parturition has not been established but evidence suggests that it has a potential role as an oxytocic in cases of therapeutic abortion. In the area of human fertility, the physiologic role of PGs in seminal fluid is hypothesized to facilitate the migration of spermatozoa from the vagina into the uterine cavity. Karolinska Institute researchers have found that some infertile males have low PG levels in their ejaculates and are now working with methods of improving the PG levels to improve their fertility. Pickles et al. proposed a potential role for PGs in the etiology of dysmenorrhea, having found a significantly higher ratio of PGF to PGE in a series of patients with severe dysmenorrhea than in a comparable series of normal patients. The luteolytic and antinidatory effects of PGF2alpha are being investigated and studies appear encouraging. PGs have therapeutic potentials in induction of labor, treatment of infertility, morning-after conception, treatment of dysmenorrhea, and contraception by alteration of fallopian tube motility.
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PMID:The role of prostaglandins in reproductive physiology. 491 53

The interrelationship of several physiological receptors which influence the hydroosmotic response of the toad urinary bladder was studied employing neurohypophyseal peptides, prostaglandin E(1), theophylline, and cyclic nucleotides. The binding property of agonists (pD(2)), synergists (pS(2)), competitive antagonists (pA(2)), and noncompetitive antagonists (pD(2)') was determined after a suitable methodology had been developed. A series of neurohypophyseal peptides was examined in detail for their catalytic activity. It was found that the replacement of the hydroxy radical of the tyrosine residue in oxytocin by a methoxy and then by an ethoxy radical led to a progressive decline in the catalytic activity of the hormone-corresponding to a change from agonist to partial agonist to competitive antagonist. [4-Leucine]-mesotocin behaved as a competitive antagonist of oxytocin. Prostaglandin E(1) (PGE(1)) was found to be a noncompetitive inhibitor of neurohypophyseal peptides and theophylline; whereas the maximal hydroosmotic response of the bladder to [2-O-methyltyrosine]-oxytocin and theophylline was greatly depressed by PGE(1), the response to saturating concentrations of oxytocin was only slightly diminished-a finding which reveals a "receptor reserve" for oxytocin. Saturating concentrations of [2-O-ethyltyrosine]-oxytocin, inactive per se, potentiate theophylline-disclosing a "threshold phenomenon" for the mediation of neurohypophyseal hormone action. It is concluded that neurohypophyseal peptides are capable of producing graded effects on adenyl cyclase both below and above the range of enzyme activity which evokes graded changes in membrane permeability.
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PMID:Threshold and receptor reserve in the action of neurohypophyseal peptides. A study of synergists and antagonists of the hydroosmotic response of the toad urinary bladder. 543 69

In the carrageenin-induced granuloma of rats the inflammatory tissue growth and macrophage invasion on the one hand and the cyclic-AMP content of the macrophages on the other, display opposite directional changes. Macrophages, isolated from this tissue at different stages of inflammation, were used to examine the effect of prostaglandin E2 on intracellular levels of c-AMP. It appears that during infiltration of the macrophages into the inflammatory tissue, the sensitivity of adenylate cyclase to activation by PGE2 increases. Arguments are presented that these observations made in vitro, are in direct relevance to the previous described anti-inflammatory effect of PGE on granuloma tissue in vivo.
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PMID:Prostaglandin E2 elevation of cyclic-AMP in granuloma macrophages at various stages of inflammation: relevance to anti-inflammatory and immunomodulatory functions. 627 Jul 40

Endogenous adenosine 3',5' -monophosphate (cAMP) levels in mastocytoma P-815 cells, synchronized either at the G1/S transition by amethopterin- or double thymidine-block or in mitosis by colcemid block, were highest during late S and early G2 phases and lowest during mitosis. These cell cycle-dependent changes in cAMP levels were largely accounted for by changes in adenylate cyclase and phosphodiesterase activities. Similar fluctuations occurred simultaneously with specific prostaglandin E1 (PGE1) binding, histidine decarboxylase activity, histamine content, and [35S]SO-2(4) incorporation into glycosaminoglycans of the cells. In addition, endogenous levels of the E group of prostaglandins (PGEs) and "14C]carachiodonic acid incorporations into PGE, phosphatidylcholine and phosphatidylinositol also exhibited fluctuation patterns similar to that of cAMP levels. Since cAMP levels still fluctuated in a serum-depleted medium where DNA synthesis and cell division were inhibited, endogeneous levels of prostaglandin and cAMP appeared not to be regulated solely by serum factor(s). Exposure of cells at G1/S transition to 1-methyl-3-isobutylxanthine (MIX) resulted in 10-fold elevation of cAMP levels throughout the cell cycle without affecting DNA synthesis. On the other hand, PGE1 and/or MIX added at late S phase elevated cAMP levels, prolonged C2 phase and retarded the cell division, but these agents added at the beginning of mitosis elevated cAMP levels without affecting the cell division. These results suggest that prostaglandin newly synthesized by the increased metabolism of phospholipids promote the cAMP synthesis via their binding to the receptors and thereby control the division and phenotypic expression of mastocytoma P-815 cells.
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PMID:Cell cycle specific fluctuations of adenosine 3',5' -monophosphate and prostaglandin binding in synchronized mastocytoma P-815 cells. 627 39

The anti-inflammatory effects of E-prostaglandins (PGE) are attracting interest because they are mediated through actions on cells which are also targets for the putative immunomodulator functions of PGE. In the majority of experimental inflammatory conditions, in which inhibitory effects of PGE have been demonstrated, a variety of immunocytes are implicated, including diverse lymphocyte populations. The inhibitory effects of PGE, however, are also readily observable on the tissue component of the carrageenin-induced granuloma (an immune-related inflammatory model) in which activated macrophages, but not lymphocytes participate. Granuloma-derived macrophages are particularly interesting cells for the study of responsiveness to PGE, because the results obtained on such cells in vitro are directly related to the anti-inflammatory effects of PGE on the macrophage phase of the granuloma in vivo. Such combined studies have revealed differences between the responsiveness of granuloma macrophages to PGE2 and prostacyclin, while with elicited peritoneal macrophages such a difference could not be observed. The adenylate cyclase in granuloma macrophages appears to be unusually sensitive to activation by PGE2, but insensitive to prostacyclin.
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PMID:Macrophages as targets of inhibitory effects of E-type prostaglandins in immune-related inflammation. 628 Apr 64


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