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Cold acclimation induces desensitization to adenosine in brown fat cells without changing receptor binding
L Unelius1, N Mohell, J Nedergaard
1Wenner-Gren Institute, University of Stockholm, Sweden.
The American Journal of Physiology
|May 1, 1990
Summary
Cold acclimation desensitizes brown fat cells to adenosine, impairing their metabolic response. This desensitization is not due to altered adenosine receptors or Gi protein coupling, suggesting a mechanism at the Gi protein-adenylate cyclase interaction.
Area of Science:
- Metabolic Physiology
- Cellular Signaling
- Adrenergic Signaling
Background:
- Brown adipose tissue (BAT) plays a crucial role in non-shivering thermogenesis.
- Adenosine signaling modulates BAT activity and energy expenditure.
- Cold acclimation is known to alter BAT function, but the specific mechanisms of adenosine receptor regulation remain unclear.
Purpose of the Study:
- To investigate the effect of cold acclimation on adenosine responsiveness in hamster brown fat cells.
- To elucidate the molecular mechanisms underlying adenosine desensitization in cold-acclimated brown fat.
Main Methods:
- Measurement of oxygen consumption rates in isolated brown fat cells from control and cold-acclimated hamsters.
- Assessment of norepinephrine dose-response curves in the presence of adenosine deaminase, IBMX, and 2-chloroadenosine.
- Analysis of [3H]phenylisopropyladenosine ([3H]PIA) binding to brown fat membranes to determine receptor affinity and density.
- Investigation of guanosine triphosphate (GTP)-induced affinity changes in [3H]PIA binding.
Main Results:
- Brown fat cells from control hamsters showed expected responses to adenosine modulation, while cells from cold-acclimated hamsters exhibited significantly reduced adenosine control.
- [3H]PIA binding assays revealed no significant differences in adenosine receptor number (Bmax) or affinity (KD) between control and cold-acclimated groups.
- GTP-induced affinity reduction of [3H]PIA binding was observed in both groups, suggesting intact receptor-Gi protein coupling.
Conclusions:
- Cold acclimation induces physiological desensitization to adenosine in hamster brown fat.
- The desensitization is not mediated by changes in adenosine receptor expression or affinity.
- The findings suggest that the adenosine desensitization mechanism in cold-acclimated brown fat may involve the Gi protein-adenylate cyclase interaction.