Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The most potent compound of a series of piperidinyl indole derivatives which decrease 5-hydroxyindole acetic acid (5-HIAA) levels in rat brain-stem was chosen for further study on the neurochemistry of serotonin (5-HT) neurons. This derivative (RU 24969: 5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl) 1 H indole, succinate) exerted a dose-dependent reduction in 5-HIAA concentrations in rat forebrain and brain-stem, which was of rapid onset and lasted for at lest 4 h. The decrease in 5-HIAA was apparently due to a decrease in 5-HT turnover since RU 24969 significantly diminished 5-HTP accumulation after RO 4-4602 administration, and 5-HIAA accumulation after probenecid treatment. Basal or 5-HT-stimulated adenylate cyclase activities in colliculi from new-born rats were unaffected by RU 24969. This compound increased serum prolactin and corticosterone levels in a dose-related manner. Together with previous behavioral observations and the potent displacement of [3H]-5-HT binding obtained with this series, the present data indicate that these new piperdinyl indole derivatives are likely potent 5-HT receptor agonists in rat brain.
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PMID:Biochemical assessment of the central 5-HT agonist activity of RU 24969 (a piperidinyl indole). 615 75

The activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by vasoactive intestinal peptide (VIP) was used as a model to investigate the molecular mechanisms triggered by the occupancy of dopamine recognition sites in rat anterior pituitary. Dopamine failed to change the basal enzyme activity, but it inhibited the stimulation of adenylate cyclase elicited by VIP. Apomorphine, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene, and 2-bromo-alpha-ergocryptine mimicked the effect of dopamine, whereas (-)-sulpiride and and classical neuroleptics antagonized it. Dopamine failed to modulate the activation of pituitary adenylate cyclase by prostaglandin E1, which does not increase prolactin secretion. From these results we infer that stimulation of D-2 (dopamine) receptors may affect pituitary secretion by inhibiting the activation of anterior pituitary adenylate cyclase by VIP or other secretagogues.
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PMID:Dopaminergic modulation of adenylate cyclase stimulation by vasoactive intestinal peptide in anterior pituitary. 617 19

Granulosa cells from small follicles were cultured as suspensions in spinner flasks for 10 days in the absence or presence of follicle-stimulating hormone (FSH). With or without FSH, the cultured cells ultrastructurally resembled luteinized cells to different degrees. FSH increased progesterone accumulation in the culture medium. Ovine prolactin potentiated the effect of FSH in terms of the quantity of progesterone produced and the duration of accumulation. FSH increased acute human chorionic gonadotropin (hCG)-responsive progesterone secretion in short-term incubations of cultured granulosa cells. Responsiveness of FSH-cultured cells was maximal at day 4; that of control cultured cells was maximal at day 6. Adenylate cyclase activity of homogenates of cells cultured for 4, 6, or 8 days was measured. FSH induced in cultured cells an hCG sensitivity of the adenylate cyclase enzyme. These results indicate that FSH induced hCG-responsive progesterone secretion and hCG-responsive adenylate cyclase activity that correlate with ultrastructural signs of luteinization and with the previously reported FSH induction of hCG receptors.
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PMID:Porcine granulosa cells in suspension culture. II. Luteinization and hCG responsiveness. 626 90

Effects of seiwhale somatotropin (STH), its biologically active fragment 77--107, porcine corticotropin (ACTH) and seiwhale prolactin on phosphodiesterase and adenylate cyclase activity of glial cells and synaptosomes isolated from the rat brain cortex were investigated. As compared with control, ACTH increased phosphodiesterase activity of glial cells by 392%, of synaptosomes by 123%, while STH by 49 and 77%, respectively, somatotropin fragment by 455 and 74%, and prolactin by 30 and 37%, respectively. Adenylate cyclase activity was significantly changed only by ACTH and only in synaptosomes (a 50% decrease). STH, its fragment and prolactin virtually failed to alter adenylate cyclase activity. The data obtained indicate that some of pituitary hormones, primarily ACTH and STH, may play the role of neuromodulators in some brain structures by decreasing the cyclic AMP level, by activating phosphodiesterase (STH and ACTH) and inhibiting adenylate cyclase (ACTH in synaptosomes).
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PMID:[Effect of pituitary hormones on phosphodiesterase and adenyl cyclase activity of brain tissue in vitro]. 626 49

Prolactin possesses positive inotropic actions in isolated heart preparations although the mechanism of this influence is not understood. Our study was designed to investigate the mechanism of this effect on the rat heart. Prolactin (50 ng/ml) produced a time-dependent increase (60%) in contractile force that reached maximum after 30 min and remained steady for a further 30 min. A similar time-dependent phenomenon was seen with 200 ng/ml prolactin although the maximum inotropic effect was reduced. Indomethacin (30 micrograms/ml) significantly reduced the inotropic effect of both prolactin concentrations although the effect of the hormone was not related to the release of 6-keto-PGF1 alpha, the prostacyclin metabolite. Propranolol (1-20 micrograms/ml) significantly reduced the positive inotropic effect of prolactin. Prolactin however had no influence on myocardial adenylate cyclase activity. Hearts that were removed from animals pretreated with 1.25 or 2.50 mg/kg reserpine did not respond to prolactin administration. It is suggested that the inotropic influence of prolactin is mediated by endogenous catecholamine liberation.
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PMID:A possible mechanism of inotropic action of prolactin on rat heart. 629 10

Defined cultures of rabbit kidney cortical collecting tubule (CCT) and cortical thick ascending limb of Henle's loop (CAL) were grown in monolayers from individual microdissected tubules and maintained for up to five passages, a maximum of 53 days. CCT cells contained cytochemically demonstrable vasopressin-stimulated adenylate cyclase, whereas CAL cells were characterized by the localization of Na+-K+-ATPase. [3H]thymidine labeling index decreased with time in primary cultures in the presence or absence of 3% serum. When added to unsupplemented serum-free media alone or in combinations, the growth factors dexamethasone, thyroxine, insulin, epidermal growth factor, and prolactin stimulated [3H]thymidine incorporation to different extents. CCT cells were maximally stimulated by addition of dexamethasone alone, whereas a combination of dexamethasone, thyroxine, insulin, and prolactin was most stimulatory for CAL cells. Addition of hormones concerned with renal ion and water transport to fully supplemented serum-free media inhibited [3H]thymidine labeling index: 1) vasopressin, isoproterenol, and dibutyryl cAMP were equally inhibitory in CCT and CAL cultures; 2) parathyroid hormone and prostaglandin E1 were more inhibitory in CAL cultures; and 3) aldosterone was particularly inhibitory in CCT cultures.
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PMID:Differential response to hormones of defined distal nephron epithelia in culture. 629 9

The responsiveness of anterior pituitary tumor (GH3) cells to promoters of prolactin secretion and/or synthesis and cyclic AMP accumulation was studied as a function of cellular Ca2+ content. GH3 cells exposed to media containing 1 mM ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid were reduced 7-fold in Ca2+ content without loss of viability. Preparations of Ca2+-depleted cells were largely unchanged in cyclic AMP content when challenged by thyrotropin-releasing hormone (TRH), whereas cells which were subsequently restored at optimal Ca2+ (0.5 mM) responded to the hormone with 2- to 3-fold increases in cyclic AMP content. The decreased responsiveness of Ca2+-depleted cells to TRH was not influenced by phosphodiesterase inhibitors, incubation time, or hormone concentration. TRH-dependent cyclic AMP accumulation was markedly potentiated by forskolin in Ca2+-restored, but not in Ca2+-depleted, cell preparations. Forskolin extended the time period during which cyclic AMP accumulated in response to TRH without altering the TRH concentration dependency of the cells. Varying increases in GH3 cyclic AMP content occurred in response to other hormones or agents which enhance prolactin secretion and/or synthesis. In Ca2+-restored cells, cyclic AMP content was increased 2-fold by prostaglandin E1 (PGE1) and epidermal growth factor (EGF), 10- to 15-fold by vasoactive intestinal polypeptide (VIP) and 6-fold by phorbol myristate acetate (PMA); the capacity of Ca2+-depleted cells, however, to accumulate cyclic AMP in response to PGE1, EGF, and VIP was greatly reduced. Accumulation of cyclic AMP following short-term incubations with cholera toxin similarly was dependent on Ca2+. Exposure of GH3 cells preloaded with 45Ca to TRH, PGE1, EGF, PMA, or VIP resulted in losses of cell-associated 45Ca. Pretreatment with these agents resulted in a decreased capacity of the cells to accumulate 45Ca from the extracellular medium. The results of this study support the hypothesis that various putative humoral regulators of prolactin secretion and/or synthesis act on GH3 cells to alter intracellular Ca2+ metabolism which in turn results in an increased cyclic AMP content through stimulation of adenylate cyclase activity.
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PMID:Regulation of Ca2+-dependent cyclic AMP accumulation and Ca2+ metabolism in intact pituitary tumor cells by modulators of prolactin production. 630 Jun 49

In male and female rat anterior pituitary homogenates dopamine inhibited basal adenylate cyclase by 30% and 50%, respectively. Dopamine also inhibited vasoactive intestinal peptide-stimulated adenylate cyclase by 50% in both sexes. Sulpiride, a specific D2 antagonist, stereospecifically blocked with high affinity the dopamine inhibition in both males and females. RU 24926, a specific, non-catechol, non-ergot D2 agonist, also inhibited basal adenylate cyclase of female pituitary with a higher apparent affinity than dopamine (KDapp 20 nM and 450 nM, respectively). This effect was also stereospecifically antagonized by sulpiride. Apomorphine was also more potent (KDapp 100 nM) than dopamine, whereas norepinephrine and SKF 38393, a specific D1 agonist, were poorly active; isoproterenol and clonidine were inactive. Ergots derivatives such as CB 154, LY 14865, pergolide, and lergotrile were potent agonists. alpha-Dihydroergocryptine was a partial agonist of the dopamine receptor negatively coupled with an adenylate cyclase. Because of the slow association kinetics of this drug with the dopamine receptor, its KDapp (0.7 nM) for adenylate cyclase inhibition could be correctly determined only after a 30-min incubation period. All classical dopaminergic antagonists blocked dopamine inhibition of pituitary adenylate cyclase, pimozide (KI 1 nM) and spiperone (KI 0.8 nM) being the more potent. There were good correlations between the affinities of large series of agonists and antagonists for the anterior pituitary dopamine receptors negatively coupled with an adenylate cyclase on one hand, and for either D2 dopamine receptors labeled with [3H] dihydroergocryptine or [3H]spiroperidol in both pituitary and striatum, or D2 pituitary receptors involved in prolactin secretion on the other hand. It is concluded that the pituitary dopamine receptors negatively coupled with an adenylate cyclase are the classical D2 receptors involved in prolactin secretion.
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PMID:Pharmacological characterization of the D2 dopamine receptor negatively coupled with adenylate cyclase in rat anterior pituitary. 630 29

In GH3 pituitary cell homogenates, acetylcholine (ACh) (IC50 200 nM) inhibits adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in a concentration- and GTP-dependent manner. Maximal inhibition was obtained with 10 microM ACh and corresponded to approximately a 50% decrease in basal enzyme activity. ACh inhibition is antagonized by atropine and is mimicked by muscarinic receptor agonists, but not by nicotine. ACh reduces the adenylate cyclase stimulation by vasoactive intestinal peptide (VIP), without changing its EC50. In intact GH3 cells, ACh decreases the cyclic AMP content and the rate of prolactin release in a concentration-dependent manner. When the cells are simultaneously exposed to VIP and ACh, the VIP-induced increases in cyclic AMP accumulation and prolactin release are reduced by 80% and 40%, respectively. The potency of VIP is not significantly changed by the presence of ACh, and vice versa.
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PMID:In GH3 pituitary cells, acetylcholine and vasoactive intestinal peptide antagonistically modulate adenylate cyclase, cyclic AMP content, and prolactin secretion. 631 Mar 60

The in vivo relationship was studied between these biochemical parameters which previous studies have separately implicated in the regression of hormone-dependent rat mammary tumors. Upon depletion of estrogen and suppression of prolactin levels by ovariectomy, there was a marked increase in the production of prostaglandin E2 (PGE2)(fourfold) and in the cyclic AMP (cAMP) content (twofold) in the regressing 7,12-dimethylbenz[a]anthracene-induced primary tumors. These two parameters appeared to be coupled since, in addition to this correlation, PGE2 stimulated adenylate cyclase and raised cAMP levels in both this primary tumor system and in another hormone-dependent transplantable rat mammary tumor (MTW9-A). Furthermore both the sensitivity of the adenylate cyclase system to PGE2 and the number of membrane binding sites for PGE2 increased upon induction of regression in these tumors. Under conditions where PGE2 and cAMP were elevated, (i.e., in regressing, but not growing, hormone-dependent mammary tumors), there was significant phosphorylation in the intact tissue of a 75,000-dalton nuclear protein, which appeared to be identical to the regression-associated protein shown by Cho-Chung and co-workers to undergo increased phosphorylation in response to elevated cAMP levels.
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PMID:Concurrent changes in growth-related biochemical parameters during regression of hormone-dependent rat mammary tumors. 631 51


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