Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In FRTL-5 thyroid cells, extracellular ATP, a P2-agonist, not only stimulates phospholipase C but also inhibits forskolin- or thyrotropin (TSH)-induced stimulation of adenylate cyclase in a pertussis toxin-sensitive manner [Okajima, Sato, Nazarea, Sho, & Kondo (1989) J. Biol. Chem. 264, 13029-13037]. We have now found that, in pertussis toxin-treated cells, ATP can directly stimulate adenylate cyclase. Although adenylate cyclase modulation occurs through ATP metabolites such as AMP and adenosine, we show that extracellular ATP itself also regulates cyclic AMP production, based on the following: (1) the actions of ATP were imitated by hydrolysis-resistant ATP analogues, (2) the elimination of adenosine by adenosine deaminase decreased the effect of ATP only partially, at least at concentrations greater than 10 microM-ATP, and (3) the amount of AMP produced from ATP was too low to account for the ATP effects. To identify the respective receptors for the three different actions of ATP, we established an antagonist profile. Suramin, which has been reported to be a P2-receptor antagonist, inhibited ATP-induced phospholipase C activation in a competitive fashion, but did not affect ATP-induced adenylate cyclase modulation. On the other hand, 8-cyclopentyl-1,3-diphenylxanthine competitively antagonized both the stimulatory and inhibitory ATP actions on cyclic AMP levels, but did not influence the activation of phospholipase C by ATP. The order of potency for various xanthine derivatives was clearly different with respect to their antagonistic effects on the stimulation and inhibition of adenylate cyclase induced by ATP. We conclude that ATP activates three receptors, each of which is coupled to a different signal transduction system in FRTL-5 cells, i.e. phospholipase C activation, and adenylate cyclase activation and inhibition.
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PMID:Extracellular ATP stimulates three different receptor-signal transduction systems in FRTL-5 thyroid cells. Activation of phospholipase C, and inhibition and activation of adenylate cyclase. 131 67

Adenosine inhibits TSH-stimulated [3H]thymidine incorporation into DNA in FRTL5 thyroid follicular cells by both inhibiting cAMP generation and acting at a locus beyond adenylate cyclase. On the other hand, adenosine markedly potentiates DNA synthesis in FRTL5 stimulated by insulin-like growth factor-I (IGF-I). The mechanisms of this latter effect are unknown, but require the coincubation of adenosine and IGF-I and not mediated by an increase in intracellular cAMP concentration. Adenosine increases the maximal response of FRTL5 to [3H]thymidine incorporation stimulated by IGF-I and increases the sensitivity of FRTL5 to IGF-I. These effects of adenosine are reflected by an increase in nuclear labeling as well as by an increase in [3H]thymidine incorporation into DNA. Adenosine also plays a role as an autocrine growth factor in FRTL5, since adenosine deaminase increases the response of these cells to TSH. The effects of adenosine on both TSH- and IGF-I-stimulated DNA synthesis are shared by guanosine and inosine, although with different potencies for the various guanine nucleosides. Inosine potentiates IGF-I-stimulated DNA synthesis, but inhibits TSH-stimulated DNA synthesis only weakly. Adenosine interacts with multiple receptors and with multiple postreceptor pathways in FRTL5 to produce divergent effects on the control of cell replication by two growth factors (TSH and IGF-I) that act through different postreceptor pathways.
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PMID:Adenosine has divergent effects on deoxyribonucleic acid synthesis in FRTL5 cells: inhibition of thyrotropin-stimulated and potentiation of insulin-like growth factor-I-stimulated thymidine incorporation. 247 35

The cAMP content of guinea pig thyroid fragments was increased 2- to 3-fold by adenosine analogs, 5'-N-ethylcarboxamide adenosine (NECA), the most potent, caused half-maximal stimulation of 0.7 microM, whereas N6-phenylisopropyl adenosine was much less potent (half-maximal stimulation at 20 microM). Exogenous adenosine by itself was slightly active, and its activity was increased in the presence of adenosine deaminase or transport inhibitors. Although adenosine analogs are partial agonists compared to TSH or the diterpene cyclase activator forskolin, the fractional rate of cAMP accumulation is greater for NECA than for TSH. The stimulatory effect of NECA was antagonized by theophylline. These effects of adenosine and its analogs on cAMP formation in intact thyroid tissue are characteristic of stimulatory adenosine receptors.
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PMID:Adenosine receptor-mediated accumulation of adenosine 3',5'-monophosphate in guinea pig thyroid tissue. 628 Sep 84

Prostaglandins F1 alpha and F2 alpha, at high concentrations (greater than or equal to 28 microM) enhanced cyclic AMP accumulation in dog thyroid slices. At lower concentrations, they inhibited the cyclic AMP accumulation induced by thyrotropin (TSH), prostaglandin E1, and cholera toxin. This effect was rapid in onset and of short duration, calcium-dependent and suppressed by methylxanthines. Prostaglandin F alpha also inhibited TSH-induced secretion and activated iodide binding to proteins. These characteristics are similar to those of carbamylcholine action, except that prostaglandins F did not enhance cyclic GMP accumulation. The effect of prostaglandin F alpha was not inhibited by atropine, phentolamine and adenosine deaminase and can therefore not be ascribed to an induced secretion of acetylcholine, norepinephrine or adenosine. It is suggested that prostaglandins F act by increasing influx of extracellular Ca2+. Arachidonic acid also inhibited the TSH-induced cyclic AMP accumulation. However this effect was specific for TSH, it was enhanced in the absence of calcium and was not inhibited by methylxanthines or by indomethacin at concentrations which completely block its conversion to prostaglandin F alpha. Arachidonic acid action is sustained. This suggests that arachidonic acid inhibits thyroid adenylate cyclase at the level of its TSH receptor and that this effect is not mediated by prostaglandin F alpha or any other cyclooxygenase product.
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PMID:Effects of prostaglandins F alpha on dog thyroid cyclic AMP level and function. 628 47

The removal of extracellular, endogenously produced adenosine in isolated rat adipocytes by treatment with adenosine deaminase enhanced their responsiveness to various lipolytic agents, i.e. the response to catecholamines, glucagon, LH, TSH, and cholera toxin was elicited at concentrations that were 10-500 times lower than those required for the stimulation of lipolysis in untreated cells in vitro. The removal of adenosine from intact fat cells largely potentiated the isoproterenol-stimulated increase in cAmP level. However, a similar treatment of undissociated segments of adipose tissue failed to influence further the response to isoproterenol. These results strongly suggest that in the intact adipose tissue, adenosine and related nucleosides are absent and do not function as modulators of adenylate cyclase or lipolysis. Under these circumstances the estimated "low" physiological concentrations of the neurotransmitters in the adipose tissue are able to modulate lipid mobilization. Previous studies have shown that insulin failed to inhibit lipolysis, induced by micromolar norepinephrine concentrations, in adenosine-free adipocytes. The present study demonstrates that at physiological catecholamine concentrations, insulin is a potent antilipolytic agent.
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PMID:Evaluation of adenosine or related nucleosides as physiological regulators of lipolysis in adipose tissue. 704 12

Immunoglobulins (IgG) from patients with Graves' disease increase inositol phosphate (IP) as well as cAMP production in rat thyroid FRTL-5 cells; IgGs from normal control subjects do not. Graves' IgG-and TSH-induced IP formation is inhibited by blocking TSH receptor (TSHR) antibodies from hypothyroid patients with primary myxedema, as is the cAMP response; this suggests that the Graves' IgG are acting through the TSHR to induce both the cAMP and phosphatidyl-inositol 4,5-biphosphate signal cascades in FRTL-5 thyroid cells as in cells with recombinant TSHR. Optimal conditions for measuring the Graves' IgG-induced IP increase include a NaCl-free Hanks' Balanced Salt Solution (HBSS) buffer system and a P1 purinergic receptor agonist; the action of each is additive. Optimization by NaCl-free HBSS is similar to that observed in cAMP assays and is specific for TSH or Graves' IgG; thus, NaCl-free HBSS did not affect ATP-induced, and actually inhibited norepinephrine-induced, IP production in FRTL-5 cells. The P1 purinergic receptor agonist acts via receptor cross-talk, which also allows further optimization of cAMP assays. Thus, adenosine deaminase improves Graves' IgG-induced cAMP production by removing adenosine from the medium. Although NaCl-free HBSS improved TSH- or Graves' IgG-induced IP and cAMP production in cells with recombinant TSHR; the modulatory action of phenylisopropyladenosine was lost.
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PMID:Receptor cross-talk can optimize assays for autoantibodies to the thyrotropin receptor: effect of phenylisopropyladenosine on adenosine 3',5'-monophosphate and inositol phosphate levels in rat FRTL-5 thyroid cells. 807 7

Adenosine has been implicated in various aspects of pituitary function but little is known of its role in the regulation of thyrotrophin (TSH) release. This study examined the effects of adenosine deaminase (ADA, which provokes adenosine breakdown) and selective adenosine-receptor ligands on the secretion of immunoreactive (ir-) TSH and prolactin (PRL) by rat anterior pituitary segments in vitro. ADA (5 U/ml) stimulated the release of both hormones (P<0.01) as also did the selective adenosine A1-receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.1 & 1 nM, P<0.01); the responses to ADA were inhibited by an A1-receptor agonist, N6-cyclohexyladenosine (0.1-10 nM, P<0.01). A non-selective A1/A2-receptor agonist, N-cyclopropylcarboxamidoadenosine (1-100 nM) had mixed effects on ir-TSH release. However, the A2A-receptor selective agonist, CGS 21680 (1-100 nM) increased ir-TSH (P<0.05) and ir-PRL release (P<0.01); its effects on ir-TSH were blocked by concentrations of DPCPX (100 nM, P<0.01) sufficient to antagonize A2-receptors. These data suggest that adenosine acts via A1-receptors to tonically suppress ir-PRL and ir-TSH release but that A2A-receptor activation enhances the release of both hormones.
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PMID:Roles for adenosine A1- and A2-receptors in the control of thyrotrophin and prolactin release from the anterior pituitary gland. 993 May 81

Leptin, which is secreted from adipocytes, has a role in the regulation of appetite and energy expenditure. The thyrotropin receptor (TSH-R) was recently found in adipocytes. We examined the effects of TSH on leptin production and lipolysis in rat epididymal adipocytes. TSH decreased the concentration of leptin in the medium time (approximately 24 hours)- and dose (approximately 10(-7) mol/L)-dependently (half-maximal inhibition [IC50] approximately 10(-9) mol/L). TSH also decreased the ob mRNA level approximately 55% in adipocytes. We confirmed the presence of TSH-R mRNA in the adipocytes by reverse transcription-polymerase chain reaction (RT-PCR). TSH stimulated glycerol release dose-dependently (IC50 approximately 10(-8) mol/L) in adipocytes. This TSH-induced glycerol release was further enhanced by adenosine deaminase (ADA). In summary, TSH reduced leptin production and stimulated lipolysis in rat epididymal adipocytes. Although the pathophysiological relevance of the regulation of leptin production and lipolysis by TSH is unknown, we speculate that TSH may affect the regulation of appetite and energy expenditure in pathophysiological states.
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PMID:Thyrotropin decreases leptin production in rat adipocytes. 1059 90