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)

Adenylate cyclase activity in particulate preparations from the myocardium of rats and cats was unaffected by 3,3',5-triiodo-L-thyronine (L-T3) added in the absence of, or together with, 5-guanylylimidodiphosphate (Gpp(NH)p), a potent activator of the enzyme. Preincubation of the heart particles with Gpp(NH)p made the cyclase sensitive to L-T3 which then caused, in concentrations of 10(-8) M and higher, additional increases in enzyme activity up to about 50 per cent above the Gpp(NH)p-stimulated level. Similar effects after (GPP(NH)p treatment were produced by low concentrations of 3,3',5'-triiodo-L-thyronine (reverse T3) and 3,3',5-triiodo-D-thyronine, whereas diiodo-tyrosine, 3,5-diiodo-L-thyronine, and 3'-isopropyl-3,5-diiodo-L-thyronine were without significant effect. The stimulatory action of L-T3 on cardiac adenylate cyclase pretreated with Gpp(NH)p may help to explain some of the acute effects of thyroid hormones on the heart that have been reported in the literature.
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PMID:Stimulation of rat and cat heart adenylate cyclase by triiodothyronine in the presence of 5'-guanylylimidodiphosphate. 101 61

1. Triiodothyronine (T3; 1.0 mg/kg per day subcutaneously) was administered to 10 dogs for 14 days; 10 saline-treated dogs served as controls. T3-treated dogs showed the expected physiological responses of hyperthyroidism; further, chronotropic responses to isoprenaline in vivo were significantly increased in T3-treated dogs. 2. Beta-adrenoceptor subtype density was measured in membrane preparations by displacement of 125I-iodocyanopindolol binding by the selective beta 2-adrenoceptor antagonist, ICI 118, 551. T3 treatment led to a 93% increase in right atrial beta 1-adrenoceptor density and a 141% increase in left ventricular beta 1-adrenoceptor density; beta 2-adrenoceptor densities in right atrial, left ventricular and lung membranes were unchanged. 3. T3-treatment did not change basal or maximally stimulated adenylate cyclase activities in left ventricular membranes. 4. Thus, the cardiovascular changes in experimental hyperthyroidism in dogs were accompanied by an increased chronotropic response in vivo to isoprenaline and an increased beta 1-adrenoceptor density in atrial and ventricular membranes. However, there was no corresponding change in basal or maximal responsiveness of adenylate cyclase in ventricular membranes.
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PMID:Cardiac beta-adrenoceptor changes in experimental hyperthyroidism in dogs. 133 80

The present studies were undertaken to explore further the mechanism by which T3 increases adenylate cyclase activity and the uptake of the sugar analog 2-deoxyglucose (2-DG) in freshly isolated rat thymocytes. In studies of cells preloaded with the fluorescent probe quin-2, whose fluorescence intensity increases linearly with increases in cytoplasmic free calcium concentration [( Ca2+]i), we have now demonstrated that T3 increases [Ca2+]i in thymocytes suspended in buffer containing 1 mM Ca2+. This effect was extremely prompt, becoming evident much less than 1 min after the addition of T3 and reaching maximal values in about 5-8 min. The subsequent time course of the T3 effect was obscured by an increase in fluorescence intensity in control thymocytes not exposed to T3, beginning after about 8 min of incubation. However, the T3 effect, after reaching its peak, appeared to remain stable for about 5 min and then to decline, abating completely in 18-30 min. No effect of T3 on [Ca2+]i was observed when thymocytes were suspended in Ca2+-free medium. The effect of T3 on [Ca2+]i was concentration dependent, and as with its actions on thymocyte adenylate cyclase activity, cAMP concentration and 2-DG uptake, the lowest effective concentration of T3 was 1 nM. Among several thyronine analogs studied, L-T3 was the most potent, followed in decreasing order of potency by L-T4, D-T3, 3,5-diiodo-3'-isopropyl-L-thyronine, and D-T4. rT3, 3,5-diiodo-L-thyronine, and D,L-thyronine were without effect. l-Alprenolol alone (10 microM) produced a modest increase in thymocyte [Ca2+]i, but, as it does with the effect of T3 on cellular cAMP concentration and 2-DG uptake, it markedly inhibited or abolished the stimulatory effect of T3 on [Ca2+]i. From these observations we conclude that T3 initiates the increase in thymocyte [Ca2+]i by enhancing the influx of extracellular calcium, though the possibility that it also releases calcium from an intracellular calcium pool cannot be excluded. Since the effects of T3 on thymocyte adenylate cyclase activity, cAMP concentration, and 2-DG uptake occur subsequent to these effects on calcium metabolism and require the presence of Ca2+ in the extracellular fluid, we suggest that an increase in [Ca2+]i, due at least partly to an influx of extracellular calcium, is the initiating event in these plasma membrane-mediated responses of the rat thymocyte to T3.
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PMID:Evidence that an increase in cytoplasmic calcium is the initiating event in certain plasma membrane-mediated responses to 3,5,3'-triiodothyronine in rat thymocytes. 253 16

Thyroid hormone regulation of beta-adrenergic receptor-coupled adenylate cyclase activity was studied in rat liver and heart particulate fractions. Thyroidectomy (Tx) increased isoproterenol-stimulated cAMP accumulation in the liver and decreased it in the heart. Administration of L-thyroxine (L-T4) or L-3,3',5-triiodothyronine (L-T3) reversed these changes in both liver and heart. The changes observed in liver beta-receptor-coupled adenylate cyclase activity after Tx were similar to those reported after adrenalectomy (ADX). Thus the hypothesis was considered that these changes with altered thyroid status are produced indirectly through alteration in adrenal corticosteroids. Hydrocortisone in Tx rats decreased liver isoproterenol-stimulated adenylate cyclase activity but had no significant effect on the heart. Serum corticosterone levels were decreased significantly (by 34%) in Tx rats, as compared to euthyroid rats. Administration of L-T4 to Tx rats doubled the serum corticosterone levels. In Tx-ADX rats, L-T4 had no significant effect on liver beta-receptor-coupled adenylate cyclase. However, L-T4 significantly increased heart beta-receptor-coupled adenylate cyclase in these animals. Dexamethasone, but not deoxycorticosterone, decreased liver isoproterenol-stimulated cAMP accumulation in Tx animals to the same extent as was observed with L-T4 and hydrocortisone. Thus overall the results indicate that in the liver, as opposed to the heart, thyroid hormones regulate beta-adrenergic receptor-coupled adenylate cyclase indirectly through corticosteroids. Glucocorticoid rather than mineralocorticoid activity seems to be responsible for this regulation.
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PMID:Differential regulation of beta-adrenergic receptor-coupled adenylate cyclase by thyroid hormones in rat liver and heart: possible role of corticosteroids. 282 Aug 55

Cytosolic adenylate cyclase activity from rat seminiferous tubules is inhibited by L-triiodothyronine (L-T3). In a typical dose-response curve, using Mn-ATP as substrate, no effect is observed at 10(-10) M L-T3; about 15 to 25% inhibition is found in the range between 10(-9) and 10(-6) M L-T3 and finally a sharp enzyme inhibition is evident at increasing hormone concentrations from 10(-6) to 10(-4) M. Incubation of decapsulated testes with L-T3 leads to a decrease of intracellular cyclic AMP levels. Dose-response relationships for such effect are similar to those found for adenylate cyclase activity. In this case a clear response is observed at 10(-8) M L-T3.
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PMID:Inhibition of cyclic 3',5' monophosphate synthesis in rat testis by L-triiodothyronine. 626 Nov 15

Cytosolic adenylate cyclase activity from rat seminiferous tubules was purified by chromtography in DEAE-cellulose, hydroxylapatite and Bio-Gel A-0.5 m as well as by centrifugation in sucrose gradients. In all these purification steps, fractions with adenylate cyclase activity also contained binding activity for L-T3. Binding studies indicate the existence of two L-T3 receptor components associated to adenylate cyclase activity. The component exhibiting the highest hormone affinity has the lowest binding capacity.
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PMID:Association of triiodothyronine binding activity to soluble adenylate cyclase in testicular preparations. 724 27

The effect of thyroid hormones on the beta 3-adrenoceptor expression was studied in the preadipose 3T3-F442A cell line. As assessed by molecular and pharmacological analyses, triiodothyronine addition to differentiating 3T3-F442A cells caused a 2.3-fold increase in beta 3-adrenoceptor mRNA levels, which was correlated with a parallel induction of beta 3-adrenoceptor number and of beta 3-adrenoceptor coupling to the adenylate cyclase system. Nuclear transcription experiments showed that triiodothyronine did not significantly alter the transcription rate of the beta 3-adrenoceptor gene. By contrast, the hormone increased by 36% the half-life of beta 3-adrenoceptor mRNA. Triiodothyronine exhibited a discrete effect on beta 3-adrenoceptor expression when added to mature 3T3-F442A adipocytes. This study indicates that thyroid hormones exert a differentiation-dependent and post-transcriptional regulation of beta 3-adrenoceptor expression in adipocytes.
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PMID:Triiodothyronine regulates beta 3-adrenoceptor expression in 3T3-F442A differentiating adipocytes. 870 62