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 effect of prostaglandins and various agents on cyclic adenosine 3',5'-monophosphate generation was studied in isolated rat glomeruli. Specific activity of adenylate cyclase in the glomeruli showed a 12-fold increase over the crude homogenate and a fivefold increase over a tubular preparation. Prostacyclin (PGI2) preferentially stimulated adenylate cyclase of isolated glomeruli at a concentration as low as 10(-9) M. Prostaglandins (PGE1, PGE2, and PGA2) and parathyroid hormone (1-34 synthetic PTH fragment) increased adenylate cyclase in glomeruli with maximal stimulation at 2 X 10(-5) M and 2-4 microgram/ml, respectively. No inhibition of PGE2 on PTH stimulation was observed. Isoproterenol (2 X 10(-4) M) caused a small stimulation, while PGF2alpha, arginine vasopressin, and angiotensin II were ineffective. The presence of guanosine triphosphate in the adenylate cyclase assay enhanced basal and PGE2- and PTH-stimulated activity, but had no effect on NaF stimulation. These findings show an effect of prostaglandins and PTH on the glomerular cAMP system and raise the possibility of a physiological action of these agents on the glomerulus.
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PMID:Stimulation of adenylate cyclase in isolated rat glomeruli by prostaglandins. 72 63

It has been shown that the human fat cell adenylate cyclase is activated by prostaglandins. Of the prostaglandins tested the E-type by causing about a 3-fold increase of enzyme activity, was more effective than the F-prostaglandins. Prostaglandin A2 had no stimulatory effect. Activation by prostaglandin E1 was not influenced by beta-adrenergic blockade in contrast to stimulation by epinephrine. Pretreatment of fat cells with trypsin resulted in an abolishment of PTH-sensitivity, but had no effect on prostaglandin responsiveness. These results suggest that the human fat cell adenylate cyclase is coupled to at least three distinct types of hormone receptors.
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PMID:Adenylate cyclase of human fat cell ghosts. Stimulation of enzyme activity by prostaglandins. 90 33

Intraluteal infusion of the prostaglandin (PG) synthesis inhibitor, sodium meclofenamate (Mec) causes premature luteolysis in rhesus monkeys. To evaluate further the actions of PG synthesis inhibitors in primate luteal function, we examined the in vitro effects of Mec and another inhibitor, flurbiprofen (Flur), on PG, cAMP, and progesterone (P) production by macaque luteal tissue obtained at midluteal phase of the menstrual cycle. First, collagenase dispersed luteal cells were incubated with 0-100 microM Mec or Flur, either alone or in the presence of 10 microM arachidonic acid (AA) to assess PGF2 alpha and PGE2 synthesis. Levels of both PGF2 alpha and PGE2 were stimulated (P less than 0.05) by AA (3.3- and 5.8-fold, respectively). Maximal suppression (P less than 0.01) of basal and AA-stimulated PGF2 alpha and PGE2 synthesis was elicited by 1 microM Mec and Flur. Second, adenylate cyclase activity, measured by the conversion of alpha 32P-ATP to alpha 32P-cAMP, was monitored in luteal homogenates exposed to increasing doses of Mec and Flur either alone or with maximal stimulatory doses of hCG, PGE2, or PGI2. Mec elicited a dose-dependent reduction (P less than 0.01) in control activity (incubated with 50 microM GTP), as well as inhibiting hCG- and PG-stimulated activity. The presence of 100 microM Mec suppressed (P less than 0.01) hCG-, PGE2- and PGI2-stimulated activity to control levels, but had no effect on activity stimulated by GMP-P(NH)P or forskolin. In contrast, Flur at any dose did not alter control activity or that stimulated by hormonal or nonhormonal activators. Third, P production by dispersed luteal cells was quantified during exposure to 0, 1, and 100 microM Mec or Flur alone or with maximal stimulatory doses of hCG, PGE2, PGD2, 6 beta PGI1, PGA2, or dibutyryl cAMP (dbcAMP). All hormones and dbcAMP stimulated (P less than 0.01) P synthesis 2-3 fold over basal levels, except PGA2, which had no effect. The presence of 100 microM Mec reduced (P less than 0.01) basal P production by 62% and abolished (P less than 0.05) hCG-, PG-, and dbcAMP-induced stimulation. Conversely, neither 1 microM Mec nor either dose of Flur affected P synthesis in the absence or presence of hormones or dbcAMP. These data indicate that: 1) Mec and Flur are potent inhibitors of PG synthesis in primate luteal cells in vitro and 2) higher doses of Mec suppress PG- and gonadotropin-sensitive adenylate cyclase activity and P production.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Disparate effects of the prostaglandin synthesis inhibitors, meclofenamate, and flurbiprofen on monkey luteal tissue in vitro. 230 10

1. Membrane currents were recorded from voltage clamped Xenopus laevis oocytes, still surrounded by follicular cells, theca and enveloping inner ovarian epithelia (ovarian follicles). 2. Superfusing follicles with frog Ringer solution containing E-series prostaglandins (PGE1 or PGE2) or oxytocin (0.5-2 microM) generated slow membrane currents arising from an increase in membrane conductance to K+. 3. Follicles taken from different frogs varied greatly in responsiveness to PGE and oxytocin. For example, enclosed oocytes with good sensitivity to prostaglandins responded to 1 nM-PGE, whereas follicles from some frogs failed to respond at 5 microM. 4. Oocytes with good responsiveness to PGE also produced K+ currents to PGA1, PGA2, PGB1, 11-deoxy-PGE1 and 11-beta-PGE2, whereas PGF2 alpha, PGI2, PGD2 and 8-iso-PGE1 generally failed to elicit membrane currents. 5. Responses to PGE and oxytocin were mimicked by the adenylate cyclase activator forskolin or by intraoocyte pressure injection of cyclic nucleotides. Responses were potentiated by the phosphodiesterase inhibitors theophylline and 3-isobutyl-1-methylxanthine (IBMX). In IBMX (0.5 mM), human atrial natriuretic factor (ANF) (10-60 nM) elicited a similar K+ conductance. This all implied that cyclic nucleotides played a role in the receptor-channel coupling mechanism of these responses. 6. Defolliculating oocytes effectively abolished responses to prostaglandins, oxytocin and ANF, suggesting that the currents arise in follicular cells. 7. The responses of PGE, oxytocin and ANF thus resembled currents elicited by catecholamines, adenosine, gonadotrophins and vasoactive intestinal peptide (VIP). However, PGE, oxytocin and ANF responses were not blocked by catecholaminergic or purinergic antagonists. Moreover, when comparing follicles isolated from different frogs, the sensitivity to PGE and oxytocin varied independently of that to gonadotrophin or VIP. These experiments suggest that Xenopus ovarian follicles contain specific and distinct receptors for PGE, oxytocin and ANF. 8. Acetylcholine attenuated the cyclic nucleotide-mediated K+ responses, including currents elicited by PGE, oxytocin and ANF. Attenuation was not dependent on, or mimicked by, activation of the inositol phosphate-diacylglycerol messenger pathways located in the oocyte itself, nor was it appreciably blocked by loading follicle-enclosed oocytes with 0.1-1.5 mM-EGTA.
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PMID:Membrane currents elicited by prostaglandins, atrial natriuretic factor and oxytocin in follicle-enclosed Xenopus oocytes. 248 34

In the present paper we have examined the properties of the prostaglandin E (PGE) receptor in a transplantable rat Leydig cell tumour (H-540). It appears that PGE1 and PGE2 share a common receptor in membrane particles from this Leydig cell tumour. From saturation analysis and modified Hofstee plots, the specific binding sites for PGE1 can be divided into a high (25%) and low affinity state (75%) with apparent equilibrium constants of dissociation (Kd) of 2.4.10(-7) mol/l and 4.4.10(-6) mol/l, respectively. Association rate kinetics at different temperatures employing 5.10(-9) mol/l [3H]PGE1 showed that specific binding was time- and temperature-dependent. At 37 degrees C an apparent steady state was achieved after approximately 4 h incubation. The binding of [3H]PGE1 was very tight and no dissociation was observed at 20 degrees C during the first 20 h. The free PGE1 receptor appears to be very unstable. Binding was reduced rapidly by storage at 0 degrees C, by freezing and thawing of membrane particles, and by incubation of concentrated membrane particles. Specificity curves showed that PGA1 and PGA2 displaced [3H]PGE1 from receptor to a somewhat lesser degree than PGE2 and PGE1, whereas PGs of the B, D, I and F series had little or no effect. The fact that inhibition of [3H]PGE1 binding by cold PGE1 occurred in the same concentration range as PGE1 activation of adenylate cyclase, indicates that the specific binding of PGE observed here represents functional receptors coupled to the adenylate cyclase.
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PMID:A transplantable rat Leydig cell tumour. Properties of the prostaglandin E receptor. 254 91

The role of adenosine 3',5'-cyclic monophosphate (cAMP) and sodium butyrate in modifying the effect of heat on murine neuroblastoma cells (NBP2) in culture was evaluated on the criterion of survival. An elevation of cellular cAMP level by prostaglandin (PG) A2, a stimulator of adenylate cyclase, and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-1724), an inhibitor of cyclic nucleotide phosphodiesterase, only during heat treatment (43 degrees C and 40 degrees C) was sufficient to enhance the effect of heat. The extent of enhancement (additive versus synergistic) depended upon the cAMP stimulating agent and the experimental condition. When these agents were added after heat treatment for the entire observation period, they produced similar results. PGA2 and R020-1724 are known to increase the intracellular level of cAMP in these cells by three and fivefold, respectively; therefore, the effect of these agents in enhancing the heat-response may be mediated by cAMP-dependent mechanisms. The presence of sodium butyrate during heat treatment alone was ineffective; however, when it was added before or after heat treatment for the entire observation period, the survival of heated cell was markedly reduced.
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PMID:Modification of the hyperthermic response on neuroblastoma cells by cAMP and sodium butyrate. 301 39

Alpha tocopheryl succinate treatment (6-8 micrograms/ml), which inhibited the growth of murine neuroblastoma (NBP2) cells (46 +/- 3%), reduced basal and prostaglandin (PG)E1- and PGA2-stimulated adenylate cyclase (AC) activity in vitro. It also inhibited sodium fluoride (NaF)- and forskolin-stimulated AC activity, suggesting that the effect of vitamin E succinate on AC activity is mediated via stimulatory GTP-binding protein (Gs) and catalytic subunit. Vitamin E succinate-induced reduction of AC activity is not strictly related to inhibition of cell growth. This is substantiated by the finding that, although retinoic acid and butylated hydroxyanisole reduced the growth by over 50%, they did not inhibit AC activity. On the other hand, 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-1724, 200 micrograms/ml), which inhibited growth (73 +/- 3%) and induced differentiation in NB cells, increased basal and PGE1-stimulated AC activity. Vitamin E succinate treatment also reduced PGE1- and PGA2-AC activity in murine fibroblasts (L-cells) without inhibiting growth.
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PMID:Effect of alpha tocopheryl succinate on adenylate cyclase activity in murine neuroblastoma cells in culture. 320 80

Detailed analysis of the action of prostaglandins (PGs) on the corpus luteum in primate species is very limited. In this study we examined the response of the adenylate cyclase system to PGs in homogenates prepared from the corpus luteum of rhesus monkeys at midluteal phase of the menstrual cycle. The conversion of [alpha 32p] ATP to [32p] cyclic AMP (cAMP) was assessed in the absence (control activity; 50 microM GTP) and presence of various concentrations of seven PGs and arachidonic acid, either alone or in combination with 250 nM hCG. Cyclic AMP production increased up to three-fold in the presence of PGD2, PGE2, PGI2 or PGF2 alpha; however PGA2, PGB2, 13, 14-dihydro-15-keto PGE2 and arachidonic acid alone did not alter cAMP levels. In dose-response studies, adenylate cyclase was 10 and 100-fold more sensitive to PGD2 (Vmax at 1 X 10(-5) M) than to PGE2 or to PGI2 and PGF2 alpha, respectively. Activity in the presence of hCG plus either PGD2, PGE2, PGI2 or PGF2 alpha did not differ from that for hCG (or the PG) alone. In contrast, addition of PGA2 or arachidonate inhibited (p less than 0.05) hCG-stimulated cAMP production by 50 and 100 percent. We conclude that the gonadotropin-sensitive adenylate cyclase of the macaque corpus luteum is also modulated by several PGs. These factors may either mimic (e.g., PGD2, PGE2, PGI2) or suppress (PGA2) gonadotropin-stimulated cAMP production and possibly cAMP-mediated events in luteal cells.
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PMID:Stimulatory and inhibitory effects of prostaglandins on the gonadotropin-sensitive adenylate cyclase in the monkey corpus luteum. 367 34

D-alpha tocopheryl succinate (vitamin E succinate), which is known to induce differentiation and growth inhibition in murine B-16 melanoma cells, reduced basal and melanocyte-stimulating hormone (MSH)-stimulated adenylate cyclase (AC) activity in vitro. Vitamin E succinate treatment also reduced sodium fluoride- and forskoline-stimulated AC activity of melanoma cells in vitro. Treatment of cells with vitamin E succinate (6 micrograms/ml] for a period of 24 hours was sufficient to reduce MSH-stimulated AC activity. Other forms of vitamin E, such as d1-alpha tocopheryl nicotinate, d1-alpha tocopheryl acetate, and d1-alpha tocopherol, which did not affect growth or morphology of melanoma cells, were relatively less effective in altering basal and MSH-stimulated AC activity. Retinoic acid, which inhibited the growth of B-16 melanoma cells, also reduced basal and MSH-, NaF-, and forskolin-stimulated AC activity in vitro. Prostaglandin A2, which inhibited growth and altered morphology, did not change basal or MSH-stimulated AC activity. These results show that one of the mechanisms of action of vitamin E succinate and retinoic acid on melanoma cells may involve reduction of basal and MSH-sensitive AC activity, and this vitamin effect is not necessarily related to growth inhibition.
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PMID:Alpha tocopheryl succinate inhibits melanocyte-stimulating hormone (MSH)-sensitive adenylate cyclase activity in melanoma cells. 369 13

Biologically active [3H]prostaglandin E2 (PGE2) bound rapidly and specifically to membrane fractions from hog fundic mucosa. Optimal binding occurred in the 30,000-g membrane preparation at 37 degrees C (pH 5.0). Scatchard analysis of specific PgE2 binding revealed the presence of a heterogeneous population of binding sites with Kd values and binding site concentrations of approximately 1 X 10(-9) M and 1 fmol/mg prot and 2 X 10(-8) M and 20 fmol/mg prot, respectively. Specific binding was inhibited by the following agents in descending order of potency: PGE1, PGA2, PGD2, 6-keto-PGF1 alpha, and thromboxane B2. Trypsin treatment or boiling reduced or abolished specific PGE2 binding. PGE2 stimulated cAMP formation in the 2,500-g fraction, with an approximate Km of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not b of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not b of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not be localized in these fractions in vitro.
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PMID:Prostaglandin E2-binding sites and cAMP production in porcine fundic mucosa. 627 6


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