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)

The effects of adenosine deaminase and of pertussis toxin on hormonal regulation of lipolysis were investigated in isolated human fat cells. Adenosine deaminase (1.6 micrograms/ml) caused a two-to threefold increase in cyclic AMP, which was associated with an increase in glycerol release averaging 150-200% above basal levels. Clonidine, N6-phenylisopropyladenosine, prostaglandin E2, and insulin caused a dose-dependent inhibition of glycerol release in the presence of adenosine deaminase. Pretreatment of adipocytes with pertussis toxin (5 micrograms/ml) for 180 min resulted in a five- to sevenfold increase in cyclic AMP. Glycerol release was almost maximal and isoproterenol caused either no further increase or only a marginal additional increase of lipolysis after pretreatment with pertussis toxin, whereas cyclic AMP levels were 500 times higher than in controls. The effects of antilipolytic agents known to affect lipolysis by inhibition of adenylate cyclase activity, i.e., clonidine, N6-phenylisopropyladenosine, and prostaglandin E2, were impaired. In contrast, the antilipolytic action of insulin was preserved in adipocytes pretreated with pertussis toxin. As in controls, the peptide hormone had no detectable effect on cyclic AMP after pertussis toxin treatment. The findings support the view that the antilipolytic effect of insulin does not require adenylate cyclase or phosphodiesterase action. In addition, the results demonstrate that, upon relief of endogenous inhibition, human fat cell lipolysis proceeds at considerable (adenosine deaminase) or almost maximal (pertussis toxin) rates. A certain degree of inhibition, therefore, appears to be necessary for human fat cell lipolysis to be susceptible for hormonal activation.
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PMID:Human fat cell lipolysis is primarily regulated by inhibitory modulators acting through distinct mechanisms. 299 84

The effect of various adrenergic drugs on the free fatty acid (FFA) output from bone marrow was studied in dog tibia after constant flow autoperfusion of the nutrient artery by femoral arterial blood and cannulation of the nutrient vein. Clonidine, an alpha-2 adrenoceptor agonist, inhibited the isoproterenol-induced FFA outflow from bone marrow adipose tissue. This effect was suppressed by the alpha-2 antagonists (phentolamine and yohimbine). Moreover, clonidine inhibited the FFA outflow initiated by theophylline associated with adenosine deaminase. When the alpha-2 sites were blocked by phentolamine or yohimbine, epinephrine exerted an enhanced effect on FFA outflow in comparison with its effect when infused alone. These in vivo experiments clearly demonstrate that alpha-2 adrenoceptor stimulation is able to inhibit beta-stimulated or theophylline plus adenosine deaminase-promoted lipid mobilization from bone marrow fat stores. The simultaneous stimulation of alpha-2 and beta adrenoceptors initiated by epinephrine could be responsible for the weaker lipid-mobilizing effect of the endogenous catecholamine. It is concluded that adrenoceptors are operative in bone marrow adipose tissue and control FFA outflow in physiological conditions. Moreover, the existence of an interplay between alpha-2 and beta adrenergic effects in in vivo conditions is demonstrated.
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PMID:Interplay of alpha-2 and beta adrenoceptors in the control of free fatty acid release from bone marrow adipose tissue. 608 78

The present communication shows the effects of several alpha-adrenergic agonists and antagonists on cyclic AMP levels in hamster epididymal adipocytes. In response to ACTH (30 mU/ml) in combination with 1-methyl-3-isobutylxanthine (0.10 mM) or adenosine deaminase (1.0 micrograms/ml), cyclic AMP levels increased to a maximum by 10 min and this level was maintained for another 20 min. Elevated cyclic AMP levels were partially suppressed by the alpha-adrenergic agents clonidine, methoxamine, methyl norepinephrine and phenylephrine. The lowest effective concentration of each of these agonists required to suppress cyclic AMP levels was 10 nM clonidine; 3 microM methoxamine; 10 microM methyl norepinephrine; 10 microM phenylephrine. Clonidine and methoxamine suppressed cyclic AMP levels by nearly 65% while phenylephrine and methyl norepinephrine caused only a 30% decline. Studies of the relative potencies of alpha-adrenergic blocking drugs on prevention of the inhibitor effect of clonidine on cyclic AMP levels disclosed that phentolamine and yohimbine were more potent blockers of clonidine action than phenoxybenzamine and prazosin. The rank order of potencies of agonists at causing suppression of cyclic AMP levels and the rank order of potencies of antagonists of clonidine action suggest similarity of the alpha-adrenergic receptors present on hamster adipocytes, which affect cyclic AMP accumulation to alpha-2 adrenergic receptors.
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PMID:Alpha-adrenergic inhibition of cyclic AMP accumulation in hamster adipocytes. Similarity of receptor with alpha-2 adrenergic receptors. 615 28