RGD Reference Report - Tonic activity of the rat adipocyte A1-adenosine receptor. - Rat Genome Database

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Tonic activity of the rat adipocyte A1-adenosine receptor.

Authors: Liang, HX  Belardinelli, L  Ozeck, MJ  Shryock, JC 
Citation: Liang HX, etal., Br J Pharmacol. 2002 Mar;135(6):1457-66.
RGD ID: 1625291
Pubmed: PMID:11906959   (View Abstract at PubMed)
PMCID: PMC1573251   (View Article at PubMed Central)
DOI: DOI:10.1038/sj.bjp.0704586   (Journal Full-text)

1. Adipocyte A(1)-adenosine receptors (A(1) AdoR) tonically inhibit adenylyl cyclase and lipolysis. Three potential explanations for tonic activity of A(1)AdoR of rat epididymal adipocytes were investigated: high affinity of adenosine for the receptor, efficient coupling of receptor activation to response, and spontaneous activity of the receptor in the absence of agonist. 2. The affinity of adenosine for the adipocyte A(1)AdoR was determined as 4.6 microM by analysis of effects of an irreversible receptor antagonist on agonist concentration-response relationships. In contrast, the potency of adenosine to decrease cyclic AMP in isolated adipocytes was 1.4 nM. 3. Occupancy by agonist of the A(1)AdoR was efficiently coupled to functional response (decrease of adipocyte cyclic AMP content). Activation by adenosine of less than 1% of A(1)AdoRs caused a near-maximal decrease of cyclic AMP in adipocytes. Thus the receptor reserve for adenosine to decrease cyclic AMP content of adipocytes was greater than 99%. 4. Affinities and receptor reserves for other A(1)AdoR agonists were determined. Agonists appeared to differ more in their affinity for the receptor than in their intrinsic efficacy to activate it. 5. A(1)AdoRs were inactive in the absence of agonist. 6. It is concluded that adipocyte A(1)AdoR are tonically activated by endogenous adenosine at nanomolar concentrations. The expression of a high density of A(1)AdoR that are efficiently coupled to a functional response enables the adipocyte to respond with high sensitivity to the low-affinity agonist, adenosine. Adipocytes may be a model for cells whose functions are tonically modulated by adenosine present in the interstitium of well-oxygenated tissues.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
purine nucleoside binding  IPIadenosine1625291 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Adora1  (adenosine A1 receptor)


Additional Information