Article date: October 2008
By: R A Ngala, J O'Dowd, S J Wang, A Agarwal, C Stocker, M A Cawthorne, J R S Arch in Volume 155, Issue 3, pages 395-406
Background and purpose:
Picomolar concentrations of the β3‐adrenoceptor agonist BRL37344 stimulate 2‐deoxyglucose uptake in soleus muscle via undefined receptors. Higher concentrations alter uptake, apparently via β2‐adrenoceptors. Effects of BRL37344 and β2‐adrenoceptor agonists are compared.
Experimental approach:
Mouse soleus muscles were incubated with 2‐deoxy[1‐14C]‐glucose, [1‐14C]‐palmitate or [2‐14C]‐pyruvate, and BRL37344, β2‐adrenoceptor agonists and selective β‐adrenoceptor antagonists. Formation of 2‐deoxy[1‐14C]‐glucose‐6‐phosphate or 14CO2 was measured. 2‐Deoxy[1‐14C]‐glucose uptake and β‐adrenoceptor mRNA were measured in C2C12 cells.
Key results:
10 pM BRL37344, 10 pM clenbuterol and 100 pM salbutamol stimulated 2‐deoxyglucose uptake in soleus muscle by 33–54%. The effect of BRL37344 was prevented by 1 μM atenolol but not by 300 nM CGP20712A or IC3118551, or 1 μM SR59230A; that of clenbuterol was prevented by ICI118551 but not atenolol. 10 nM BRL37344 st4mulated 2‐deoxyglucose uptake, whereas 100 nM clenbuterol and salbutamol inhibited uptake. These effects were blocked by ICI118551. Similar results were obtained in C2C12 cells, in which only β2‐adrenoceptor mRNA could be detected by RT‐PCR. 10 nM BRL37344 and 10 pM clenbuterol stimulated muscle palmitate oxidation. In the presence of palmitate, BRL37344 no longer stimulated 2‐deoxyglucose uptake and the effect of clenbuterol was not significant.
Conclusions and implications:
Stimulation of glucose uptake by 10 pM BRL37344 and clenbuterol involves different atypical pharmacologies. Nanomolar concentrations of BRL37344 and clenbuterol, probably acting via β2‐adrenoceptors, have opposite effects on glucose uptake. The agonists preferentially stimulate fat rather than carbohydrate oxidation, but stimulation of endogenous fat oxidation cannot explain why 100 nM clenbuterol inhibited 2‐deoxyglucose uptake.
DOI: 10.1038/bjp.2008.244
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