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)

Alanine and glutamine formation and release were studied using the intact epitrochlaris preparation of rat skeletal muscle. Epinephrine reduced the release of alanine and glutamine in a concentration-dependent manner. Measurable inhibition was observed at 10(-9) M epinephrine, and maximal inhibition was obtained at 10(-5) M. Norepinephrine also reduced alanine and glutamine formation and release but the concentration required for maximal inhibition was approximately 100-fold greater than for epinephrine. Isoproterenol (beta agonist), but not phenylephrine (alpha agonist), reproduced the effects of epinephrine, and propranolol (beta antagonist), but not phentolamine (alpha antagonist), blocked the effect of the catecholamine. N6,O2'-Dibutyryl adenosine 3':5'-monophosphate reproduced the effects of epinephrine and theophylline potentiated the effect of submaximal concentrations of the hormone. Glucagon and prostaglandin E2 had no observable effect on amino acid release. Insulin did not modify the inhibition of alanine and glutamine release produced by epinephrine. Alanine and glutamine formation from added precursor amino acids was unaffected by epinephrine or cyclic adenosine 3':5'-monophosphate. Epinephrine reduced alanine formation in muscles obtained from diabetic rats or animals treated with thyroxine or cortisone. These findings indicate that physiological levels of catecholamines reduce alanine and glutamine formation and release from skeletal muscle. This effect is mediated by a beta-adrenergic receptor and the adenylate cyclase system and can be accounted for by an inhibition of muscle protein degradation.
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PMID:Alanine and glutamine synthesis and release from skeletal muscle. IV. beta-Adrenergic inhibition of amino acid release. 17 62

Many hormones initiate their biologic actions by augmenting the intracellular concentrations of 3',5'-adenosine monophosphate (cyclic AMP). The nucleotide has been found in body fluids; its determination in plasma and urine can be performed by a rapid, simple and specific method: the cyclic AMP assay kit of the Radiochemical Centre (Amersham, England). The assay is based on the competition between unlabelled cAMP and a fixed quantity of the tritium labelled compound for binding to a bovine muscle protein which has a high specificity and affinity for cAMP. Different factors must be considered in evaluating the 24 h urinary content of the nucleotide: the renal or extrarenal origin of cAMP and the functional status of the kidneys. In basal conditions the urinary cAMP excretion is significantly correlated with creatinine excretion (n = 67; r = 0.47; p less than 0.001) thus confirming that the most part of cAMP excreted is derived from the plasma by glomerular filtration. Parathyroid hormone (PTH) stimulates adenylate cyclase predominantly in the renal cortex, whereas vasopressin (ADH) stimulated the enzyme in the medulla; thus PTH and ADH could increase the amount of cAMP in the urine from the renal source. In a case of diabetes insipidus and infusion of ADH caused a prompt rise in cAMP urinary excretion. In 5 normals an infusion of bovine synthetic parathyroid hormone caused an increased excretion of cAMP that preceded the phosphaturic response. An infusion of salmon synthetic calcitonin caused a rise in phosphate excretion and no increase in cAMP urinary content. As it concerns the two calciotopic hormones, PTH and CT, it is reasonable to assume that renal receptors are distinct. The 24 h urinary excretion of cAMP in 55 control subjects (3613 +/- 1460 D.S. n moles) was contrasted with the lower excretion in 25 elderly subjects (70-93 years: 1804 +/- 699 n moles), with the high cAMP excretion in a patient with hyperparathyroidism (that fell to normal values following removal of the parathyroid adenoma) and with the low cAMP excretion in patients with primary or surgical hypoparathyroidism. The mean 24 h cAMP excretion in patients with renal insufficiency was significantly decreased when compared to control subjects. These findings and recent reports confirm that the 24 h urinary output of cAMP may be considered an useful index of pharathyroid function in man.
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PMID:[The diagnostic value of the determination of cyclic 3',5'-adenosine monophosphate (cAMP) in urine]. 19 Jun 33

1. The Gilman (1970) procedure for determining cyclic AMP (adenosine 3':5'-cyclic monophosphate) by saturation analysis gave erroneous results when applied to the analysis of extracts of whole brain or preparations of membrane fragments from brain. 2. The extracts contained a non-diffusible factor, which enhanced the binding of cyclic AMP by the muscle protein fraction. 3. Extracts also contained material which inhibited binding, but net inhibition of binding was only observed when relatively concentrated extracts were analysed. 4. The error introduced by the factors modifying binding could be eliminated by incorporation of unlabelled internal standards in the unknowns. The design adopted enables a statistical estimate to be made of the standard error of a single assay. 5. The modified assay was used to determine bound cyclic AMP and adenylate cyclase activity in cerebral membrane fragments. Five preparations of synaptic membrane fragments contained less than 3.5pmol of cyclic AMP/mg of protein; a microsomal fraction from rat contained 65pmol of cyclic AMP/mg of protein.
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PMID:Determination of adenosine 3':5'-cyclic monophosphate in cerebral tissues by saturation analysis. Assessment of a method using a binding protein from ox muscle. 434 52

Clofibrate is a hypolipidemic agent that causes muscle protein breakdown in rats, and an acute muscular syndrome in man. It also inhibits adenylate cyclase in fat tissue. Muscle protein metabolism has been shown to be regulated by cyclic nucleotides. In the present experiments were measured several parameters of cyclic nucleotide metabolism to determine the role that cyclic nucleotides play in clofibrate-induced muscle protein degradation. It was found that clofibrate treatment did not alter cyclic nucleotide levels, nor did it change the activities of basal or hormone-stimulated adenylate cyclase, or cyclic nucleotide phosphodiesterase in muscle. Our results suggest that muscle protein breakdown in clofibrate-treated rats is not regulated by cyclic nucleotides.
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PMID:Clofibrate does not alter cyclic nucleotide metabolism in muscle. 613 74

Epitrochlearis muscles obtained from normal male Sprague-Dawley rats used as controls (C) and rats with reduced renal mass (Nx) were incubated for 1 hr in Krebs-Ringer buffer containing 5 mM glucose with or without insulin, 25-hydroxycholecalciferol [25(OH)D3] or 1,25 dihydroxycholecalciferol [1,25(OH)2D3]. Plasma levels of 25(OH)D3 were unaffected by reduction in renal mass. Alanine (ALA), tyrosine (TYR), and phenylalanine (PHE) release rates from muscles of Nx rats were increased 40% above C values. Addition of 100 ng/ml of 25(OH)D3 to the incubating media reduced these release rates to C values within 1 hr of incubation. No additive effects with insulin were seen. Addition of 1 ng/ml of 1,25(OH)2D3 did not affect these results. Reduction of renal mass or the addition of insulin or 25(OH)D3 did not affect tissue concentrations of ATP or phosphocreatine. On the other hand, tissue levels of TYR and PHE were increased significantly (approximately equal to 20 to 25%) in muscles from Nx rats compared to C values and were reduced to control values by the addition of 25(OH)D3. The addition of insulin to the incubating media reduced the tissue levels of TYR and PHE in muscles of C rats by approximately equal to 20%, but reduced these levels in muscles of Nx rats by approximately equal to 55%. 25(OH)D3 did not affect tissue levels of cyclic AMP in muscles from either C or Nx rats. Protein synthetic rates were reduced significantly in muscles from Nx rats and returned to C values after 3 hr of incubation but were unaffected by 25(OH)D3. Muscle uptake of 3H,25(OH)D3 was reduced by approximately equal to 30% in muscles from Nx rats compared to C rats. These data suggest that increased muscle protein catabolism exists in rats with reduced renal mass which can be reduced to C values by 25(OH)D3 and does not appear to be mediated through stimulation of adenylate cyclase. 25(OH)D3 did not affect muscle protein synthetic rates. Reduced uptake of 3H,25(OH)D3 by muscles of Nx rats suggests that resistance to this vitamin metabolite may exist at the level of muscle in uremia.
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PMID:Effects of vitamin D metabolites on protein catabolism of muscle from uremic rats. 634 87