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

---

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

This study examined the platelet-aggregating and procoagulant activities of two hematogenously disseminating tumors, a mouse lymphoblastic leukemia (L5178Y) and a mouse renal adenocarcinoma (RAG). Tumor-induced human platelet aggregation was inhibited by addition of the following agents to platelet-rich plasma (PRP): a calcium channel blocker (verapamil), a chelator of divalent cations (EDTA), stimulators of adenylate cyclase (2-fluoroadenosine and forskolin), and inhibitors of cAMP phosphodiesterase (oxagrelate and papaverine). The platelet-aggregating activities of both cell lines were completely blocked by treatment of the cells with heat, sonication, phospholipase A2, and Triton X-100. These data suggest that L5178Y and RAG cell-induced human platelet aggregation are dependent on a heat-labile phospholipid component of the tumor cell membrane. L5178Y cells had greater platelet-aggregating activity in human plasma than in rat or mouse plasma, whereas RAG cells had greater procoagulant activity in rat or mouse plasma than in human plasma. The procoagulant activity of RAG cells in rat and mouse plasma was demonstrated by three lines of evidence: RAG cells induced heparinized PRP to clot; the thrombin inhibitor DAPA lengthened of the clotting time and the lag time before aggregation; and RAG cells shortened of the recalcification time of the plasma. The above data indicate that RAG cell-induced murine platelet aggregation and coagulation is dependent on thrombin generation.
...
PMID:Murine tumor-induced platelet aggregation and coagulation: mechanisms, inhibitors, and species differences. 359 Jan 14

Basal as well as GTP-dependent adenylate cyclase activity was partially resistant to porcine pancreatic phospholipase A2, although more activity was degraded at 16 than at 2 degrees C. In contrast, isoproterenol-dependent activity was completely destroyed regardless of the temperature. Snake venom phospholipase A2 destroyed approximately 90% of basal and GTP-dependent adenylate cyclase activity at all temperatures. The difference between the lipases is consistent with earlier evidence that elevated temperature facilitates the entry of some forms of phospholipase into the membrane bilayer. The temperature dependence of adenylate cyclase activation by the GTP analog Gpp[NH]p and its pancreatic phospholipase sensitivity were compared. The Arrhenius plots were markedly similar and biphasic with discontinuities at approximately 8 degrees C. The same temperature-dependent phospholipid phase transition might account, therefore, for both adenylate cyclase properties. Only small amounts of membrane phosphatidylethanolamine and phosphatidic acid were hydrolyzed by pancreatic phospholipase in a temperature-dependent manner analogous to adenylate cyclase degradation. These results suggest that specific phospholipids support catalysis and adenylate cyclase activation, but that different phospholipids are required for receptor coupling which may occur in a less viscous part of the membrane.
...
PMID:Phospholipase A2 sensitivity of uterine smooth muscle membrane phospholipids and adenylate cyclase activity. Effect of temperature on the action of phospholipase present in excess. 401 92

The mechanism of action of Senokot, a widely used laxative, has not been established. Senokot was given orally to rats 8-14 h before intestinal water and electrolyte transport were studied. Senokot significantly decreased colonic and jejunal water absorption measured in vivo by the single-pass perfusion technique. The Senokot changes were not associated with changes in jejunal or colonic histology or adenylate cyclase activity or colonic cyclic adenosine monophosphate content. Senokot also altered active electrolyte transport in rat descending colon as measured by the Ussing chamber-voltage clamp technique. These changes consisted of an increase in short-circuit current and a decrease in active Na and Cl transport that was due to a decrease in the mucosal-to-serosal fluxes. The changes in active electrolyte transport were dependent on Ca++ in the serosal but not the mucosal bathing solution. In contrast, addition of 10(-4) M verapamil to the serosal surface did not alter the Senokot effect. In spite of a dependence on serosal Ca++, Senokot did not alter 45Ca++ entry across the colonic serosal surface. The phospholipase A2 inhibitor quinacrine (10(-4) M) also did not alter the effect of Senokot on colonic Na and Cl transport. Senokot alters active colonic Na and Cl transport via a presently unknown mechanism that is dependent on serosal Ca++.
...
PMID:Effect of Senokot on rat intestinal electrolyte transport. Evidence of Ca++ dependence. 608 40

The interaction of two coexisting transmitters in the cat submandibular gland has been elucidated by studying effects of VIP and carbachol on cyclic AMP accumulation in isolated acini from the gland. Carbachol was found to potentiate the cyclic AMP increase induced by VIP by an atropine sensitive mechanism. The effect of carbachol on cyclic AMP accumulation was abolished by including EGTA in the incubation medium as was the carbachol mediated potentiation of VIP responses. The calmodulin inhibitor trifluoperazine had a similar, but less marked effect. The effect of carbachol was mimicked by phenylephrine (30 microM) and by the calcium inophore A 23187 (3 microM), and also by ethanol in a concentration reported to enhance membrane fluidity. The phospholipase A2 inhibitor, mepacrine, tended to decrease carbachol actions. Our results show that the potentiation of VIP responses in feline submandibular gland is calcium-dependent. The mechanism could involve a calcium-calmodulin-induced stimulation of adenylate cyclase or calcium-induced change in membrane phospholipid metabolism.
...
PMID:Calcium-dependent enhancement by carbachol of the VIP-induced cyclic AMP accumulation in cat submandibular gland. 609 14

Phospholipid composition of Tetrahymena plasma membranes was modified by phospholipase A2-treatment and its effects on the activities of the two membrane-bound cyclases (adenylate and guanylate) were studied. Phospholipase A2 from Crotalus adamanteus was found to hydrolyze preferentially phosphatidylethanolamine of isolated plasma membranes. In the phospholipase A2-treated membranes in which 45% of total phosphatidylethanolamine was converted to its lysolipid, adenylate cyclase activity was to a small extent reduced, whereas guanylate cyclase activity was decreased almost to a half. However, the stimulation rate of the guanylate cyclase activity by calmodulin was unaffected in phospholipase A2-treated plasma membranes. The apparent Km value for substrates was not different between phospholipase A2-untreated and -treated plasma membranes. The ESR analysis demonstrated that the phospholipase A2-treated plasma membranes showed an increased fluidity in the range above 25 degrees C as compared to the untreated control membranes. These results suggest that guanylate cyclase is more dependent on phospholipid environment than adenylate cyclase in Tetrahymena plasma membranes, presumably offering evidence for the different location of two enzymes in the membrane.
...
PMID:Differential inhibitory effects by phospholipase A2 on guanylate and adenylate cyclases of Tetrahymena plasma membranes. 612 36

Methylisobutylxanthine (MIX) raised cAMP levels and inhibited prostacyclin synthesis and arachidonic acid release in endothelial cells from both pig aorta and human umbilical vein. These effects were reversible and dose dependent on MIX concentrations. Dibutyryl cAMP (3 mM) alone did not inhibit prostacyclin synthesis or arachidonic acid release. When added with MIX, dibutyryl cAMP did not enhance the inhibition elicited by MIX. MIX inhibited the formation of lysophospholipids, 1,2-diacylglycerol and phosphatidic acid in bradykinin-stimulated pig endothelial cells, suggesting that the inhibition of prostacyclin synthesis resulted from an apparent inhibition of both phospholipase A2 and phospholipase C. Other phosphodiesterase inhibitors, theophylline and mopidamole, also raised cAMP levels and inhibited arachidonic acid release. However, there was no correlation between cAMP levels and these inhibitions. Forskolin, an adenylate cyclase activator, elevated intracellular cAMP levels with no apparent inhibition on prostacyclin synthesis. We conclude that the inhibitory effect of MIX on phospholipase A2 and phospholipase C is probably through mechanisms other than the elevation of the cAMP level.
...
PMID:Inhibition of prostacyclin synthesis in endothelial cells by methylisobutylxanthine is not mediated through elevated cAMP level. 619 92

Islet-activating protein (IAP) suppressed Ca2+-induced histamine release and phospholipase A2 activation in Gpp(NH)p-loaded mast cells. Since the guanine nucleotide-binding protein involved in adenylate cyclase inhibition is known to lose its function upon being ADP-ribosylated by IAP, the nucleotide-binding protein is likely to mediate Ca2+-linked biosignalling leading to histamine secretion.
...
PMID:Islet-activating protein, pertussis toxin, inhibits Ca2+-induced and guanine nucleotide-dependent releases of histamine and arachidonic acid from rat mast cells. 620 90

A variant (HS-1) of a murine macrophage cell line (P388D1) was obtained by cell cluster technique based on the Ia antigen expression induced by lymphokines. Receptors for both IgG2a and IgG2b but no detectable I-Ad are expressed on the surface of the majority of HS-1 cells. Exposure of HS-1 cell to concanavalin A supernatant or recombinant IFN-gamma resulted in the induction of I-Ad antigens on greater than 90% of the cells within 48 hr. The effects of lymphokines were transient and dependent on the synthesis of messenger RNA because the removal of lymphokines or the presence of actinomycin D both blocked Ia expression. The prior or simultaneous binding of monoclonal IgG2a or IgG2b antibodies complexed with sheep erythrocytes to respective cell surface Fc gamma R suppressed the Ia antigen inducing activity of lymphokines. Neither antibody nor antigen alone could suppress the effect of lymphokines. Inhibitors of phospholipase A2 or cyclooxygenase, which have been shown previously to suppress Fc gamma 2bR, but not Fc gamma 2aR, triggered activation of the adenylate cyclase system and reversed Fc gamma 2bR- but not Fc gamma 2aR-mediated suppression of IFN-gamma-induced Ia antigen expression.
...
PMID:Fc gamma receptor-mediated suppression of gamma-interferon-induced Ia antigen expression on a murine macrophage-like cell line (P338D1). 623 88

C6 astrocytoma cells contain beta-adrenergic receptors coupled to adenylate cyclase. A 2-hr exposure to l-isoproterenol results in an 80% decrease in cyclic AMP production in response to a subsequent challenge by l-isoproterenol (desensitization). This loss in responsiveness is paralleled by a 20-30% decrease in the apparent number of beta-adrenergic receptors and by increased release of arachidonic aciid into the medium. The increased release of arachidonic acid is caused by the action of phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) and corresponds to increased turnover of methylated phospholipids. Mepacrine and tetracaine, both inhibitors of this phospholipase A2, are able to block l-isoproterenol-induced desensitization of cyclic AMP production and the decrease in beta-adrenergic receptors. Mellitin and phorbol ester, two activators of phospholipase A2, when preincubated with the cells cause a decreased cyclic AMP response of the cells to l-isoproterenol. These results suggest that the activation of phospholipase A2 in the local domain of the beta-adrenergic receptor may be involved in desensitization.
...
PMID:Mepacrine blocks beta-adrenergic agonist-induced desensitization in astrocytoma cells. 624 90

Forced immobilization is a severe stress in rats which diminishes levels of epinephrine in specific nuclei in the hypothalamus and brain stem, suggesting that release of epinephrine is stimulated to a rate which exceeds the rate of its replacement. In the pineal gland, frog erythrocytes, C6 astrocytoma cells and rat brain, beta-adrenoceptor agonists appear to regulate the number of their receptors. Exposure to high concentrations of an agonist leads to apparent decrease in receptors reflected by a decrease in maximal specific binding of antagonists. The apparent decreases in receptors have been shown to be attended by decreases in physiologic responsiveness. In C6 astrocytoma cells, beta-agonists stimulate methylation of phosphatidylethanolamine to increase formation of membrane phosphatidylcholine which in turn appears to enhance activation of adenyl cyclase. Interference with the metabolism of phospholipids by exposure to phospholipase A2 inhibitor, mepacrine (quinacrine), prevents agonist-induced desensitization of beta-adrenoceptors in astrocytoma cells. In the present study repeated immobilization stress has been found to decrease significantly the number of beta-adrenoceptors in hypothalamus and brain stem while increasing the number of alpha 2-adrenoceptors. The desensitization of beta-adrenoceptors was prevented by treatment with mepacrine.
...
PMID:Mepacrine treatment prevents immobilization-induced desensitization of beta-adrenergic receptors in rat hypothalamus and brain stem. 625 19


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---