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

Neuropeptide Y (NPY) and peptide YY (PYY) are regulatory peptides that have considerable sequence homology with pancreatic polypeptide. Because (a) NPY has been shown to be colocalized with noradrenaline in peripheral as well as central catecholaminergic neurons, and (b) alpha 2-adrenergic receptors of adipocytes play a major role in the regulation of lipolysis, we investigated the effect of NPY and PYY on isolated fat cells. In human fat cells NPY and PYY promoted a dose-dependent inhibition of lipolysis elicited by 2 micrograms/ml adenosine deaminase (removal of adenosine) whatever the lipolytic index used (glycerol or nonesterified fatty acids). In dog fat cells NPY and PYY inhibited adenosine deaminase-, isoproterenol- and forskolin-induced lipolysis. In humans and dogs the effects of NPY or PYY were abolished by treatment of cells with Bordetella pertussis toxin, clearly indicating the involvement of a Gi protein in the antilipolytic effects. This study indicates that, in addition to alpha 2-adrenergic agonists, NPY and PYY are also involved in the regulation of lipolysis in human and dog adipose tissue as powerful antilipolytic agents. Further studies are needed to characterize the pharmacological nature of the receptor mediating the inhibitory effect of NPY and PYY in fat cells.
 ...
PMID:Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein. 210 80

This communication reports the effects of the exotoxin of Bordetella pertussis (pertussis toxin) on hamster brown fat cells. Pertussis toxin significantly increased the lipolytic and respiratory responses to isoproterenol but did not increase the basal rates of either of these processes. In contrast, the stimulation of respiration by the alpha-adrenergic agent phenylephrine was not altered by pertussis toxin. The inhibitory effects of adenosine on stimulated lipolysis, respiration, and adenylate cyclase activity were completely abolished by pertussis toxin, as was the ability of methylxanthines or adenosine deaminase to potentiate isoproterenol stimulation of respiration or lipolysis. These effects of pertussis toxin were associated with an ADP ribosylation of a single membrane protein having a molecular weight of approximately 41. These data demonstrate that pertussis toxin can prevent the inhibitory action of adenosine on brown fat cells and suggest that the effects of the nucleoside on these cells results from inhibition of adenylate cyclase. We further suggest that the enhanced responses to isoproterenol in pertussis-treated adipocytes results from a blockade of the action of endogenous adenosine. In addition to blocking adenosine action, pertussis toxin also abolished the antilipolytic effect of insulin. However, because the antilipolytic effect of insulin was prevented by adenosine deaminase and 3-isobutyl-1-methylxanthine and restored by 2-chloroadenosine, we conclude that insulin action on these cells is dependent on adenosine. Thus pertussis toxin blockade of insulin action appears to be secondary to blockade of adenosine action.
 ...
PMID:Effects of pertussis toxin treatment on metabolism in hamster brown adipocytes. 241 1

The responsiveness of lipolysis to the stimulatory agonists noradrenaline, corticotropin and glucagon and to the inhibitory agonists N6-phenylisopropyladenosine, prostaglandin E1 and nicotinic acid was investigated with rat white adipocytes incubated with a high concentration of adenosine deaminase (1 unit/ml). The cells were obtained from fed or 48 h-starved euthyroid animals or from fed or starved animals rendered hypothyroid by 4 weeks of treatment with low-iodine diet and propylthiouracil. Hypothyroidism increased sensitivity to and efficacy of all three inhibitory agonists in their opposition of noradrenaline-stimulated lipolysis. Starvation decreased sensitivity to all three inhibitory agonists when opposing basal lipolysis. Hypothyroidism decreased sensitivity to noradrenaline, glucagon and corticotropin by 37-, 4- and 4-fold respectively and decreased the maximum response to these agonists by approx. 50%, 50% and 75% respectively. Starvation reversed decreases in maximum response to these agonists in hypothyroidism. Starvation in the euthyroid state increased sensitivity to glucagon and noradrenaline, but did not alter sensitivity to corticotropin. Cells from hypothyroid rats were relatively insensitive to Bordetella pertussis toxin, which substantially increased basal lipolysis in the euthyroid state.
 ...
PMID:Sensitivity of adipocyte lipolysis to stimulatory and inhibitory agonists in hypothyroidism and starvation. 302 50

Adenosine deaminase (1 unit/ml) potentiated the lipolytic action of noradrenaline in adipocytes isolated from brown adipose tissue of 1- and 6-week-old rats by decreasing the EC50 (concn. giving 50% of maximal effect) for noradrenaline by 3-4-fold. With cells from neonatal rabbit tissue, adenosine deaminase only had a small, non-significant, effect on the EC50 for noradrenaline. Lipolysis in rat brown adipocytes was inhibited by low concentrations of N6-phenylisopropyladenosine (PIA). Rabbit cells were far less sensitive to PIA. PIA, prostaglandin E1 and nicotinate all inhibited noradrenaline-stimulated respiration in rat brown adipocytes. Hypothyroidism diminished the maximum response of respiration and lipolysis to noradrenaline in rat cells and increased the EC50 for noradrenaline. Responsiveness of lipolysis to noradrenaline was particularly decreased in hypothyroidism and was partially restored by addition of adenosine deaminase. Lipolysis in cells from hypothyroid rats was more sensitive to the anti-lipolytic action of PIA. Bordetella pertussis toxin increased lipolysis in the presence of PIA, suggesting an involvement of the Ni guanine-nucleotide-binding protein in the control of brown-adipocyte metabolism.
 ...
PMID:Effect of adenosine deaminase, N6-phenylisopropyladenosine and hypothyroidism on the responsiveness of rat brown adipocytes to noradrenaline. 380 Sep 44