title: Characterization of the adenosine receptor modulating insulin action in rat skeletal muscle.
abstract: The pharmacological profile of adenosine receptors in rat soleus muscle has been investigated by studying the effects of A1-and A2-selective adenosine receptor agonists on glucose utilization and the system A amino acid transporter under conditions where adenosine has been reported to exert a modulatory action on these insulin-sensitive processes. In the presence of adenosine deaminase and a sub-maximally effective concentration of insulin (50 microU/ml), the A1-selective agonists N6-cyclopentyladenosine and R(-)-N6-(2-phenylisopropyl)adenosine (R(-)PIA) caused concentration-dependent inhibitions of 2-deoxy[3H]glucose 6-phosphate and alpha-[14C]methylaminoisobutyric acid accumulations, but had no effect on the rate of [14C]glucose incorporation into glycogen, in incubated soleus muscle strips. These effects on glucose transport/phosphorylation and system A amino acid transport could be antagonized by 8-cyclopentyl-1,3- dipropylxanthine and 8-phenyltheophylline. The A2-selective adenosine receptor agonists CGS 21680 and 2-(phenylamino)adenosine were much less potent in their inhibition of these metabolic processes. These data support the proposal that adenosine exerts a post-receptor insulin-modulatory action in skeletal muscle and strongly suggest that this action is mediated by A1 adenosine receptors: the possible intracellular signalling mechanism(s) for this hormone-modulatory effect of adenosine are discussed.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Leicester, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Challiss
authors.forename: S J
authors.initials: SJ
authors.lastname: Richards
authors.forename: L
authors.initials: L
authors.lastname: Budohoski
mesh_terms: D000243:Adenosine Deaminase / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D058914:Purinergic Antagonists; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*
chemical_list: D000596:Amino Acids; D007328:Insulin; D007773:Lactates; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D019344:Lactic Acid; D006003:Glycogen; D000242:Cyclic AMP; D000243:Adenosine Deaminase