Cold acclimation induces desensitization to adenosine in brown fat cells without changing receptor binding.
The ability of brown fat cells isolated from control and cold-acclimated hamsters to respond to adenosine was investigated. In measurements of the rate of oxygen consumption, it was observed that cells from control hamsters responded as expected to addition of adenosine deaminase, 3-isobutyl-1-methylxanthine (IBMX), or 2-chloroadenosine (i.e., norepinephrine dose-response curves were shifted to left in presence of adenosine deaminase or IBMX and to right with 2-chloroadenosine). However, brown fat cells isolated from cold-acclimated hamsters, under identical conditions, showed almost complete absence of adenosine control. Thus acclimation to cold induced a desensitization to adenosine by physiological means. To evaluate the molecular mechanism underlying desensitization to adenosine, [3H]phenylisopropyladenosine ([3H]PIA) binding to brown fat membranes from control and cold-acclimated hamsters was investigated. [3H]PIA bound with similar high affinity (KD approximately 5 nM) and saturability (Bmax approximately 15 fmol/mg protein) in both membrane preparations, demonstrating that desensitization to adenosine was not due to changes in adenosine receptor number or receptor affinity for adenosine. Furthermore, GTP induced a reduction in [3H]PIA affinity in brown fat membranes from both control and cold-acclimated hamsters, indicating that desensitization was probably not due to an uncoupling between the receptor and Gi protein. It was therefore concluded that the adenosine desensitization process may be located at the Gi protein-adenylate cyclase interaction.
Wenner-Gren Institute, University of Stockholm, Sweden.
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Unelius
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Mohell
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Nedergaard
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015762:2-Chloroadenosine / Q000494:pharmacology; D000064:Acclimatization; D000241:Adenosine / Q000031:analogs & derivatives* / Q000502:physiology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003080:Cold Temperature; D006224:Cricetinae; D004492:Edetic Acid / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010660:Phenylisopropyladenosine / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism*
D011983:Receptors, Purinergic; D015762:2-Chloroadenosine; D010660:Phenylisopropyladenosine; D004492:Edetic Acid; D000243:Adenosine Deaminase; D008274:Magnesium; D000241:Adenosine; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine