To assess the relative roles and potential contribution of adrenergic receptor subtypes other than the ₃-adrenergic receptor in norephinephrine-mediated glucose uptake in brown adipocytes, we have here analyzed adrenergic activation of glucose uptake in primary cultures of brown adipocytes from wild-type and ₃-adrenergic receptor KO (₃-KO) mice. In control cells in addition to high levels of ₃-adrenergic receptor mRNA there were relatively low _1a-, _1D- and moderate ₁-adrenergic receptor mRNA levels with no apparent expression of other adrenergic receptors. The levels of _1a-, _1D- and ₁-adrenergic receptor mRNA were not changed in the ₃-KO brown adipocytes, indicating that the ₃-adrenergic receptor ablation does not influence adrenergic gene expression in brown adipocytes in culture. As expected the ₃-adrenergic receptor agonists BRL-37344 and CL-316 243 did not induce 2-deoxy-D-glucose uptake in ₃-KO brown adipocytes. Surprisingly, the endogenous adrenergic neurotransmitter norepinephrine induced the same concentration-dependent 2-deoxy-D-glucose uptake in wild-type and ₃-KO brown adipocytes. This study demonstrates that ₁-adrenergic receptors - and to a smaller degree ₁-adrenergic receptors - functionally compensate for the lack of ₃-adrenergic receptors in glucose uptake. ₁-Adrenergic receptors activate glucose uptake through a cAMP/protein kinase A/ PI3K pathway, stimulating conventional and novel PKCs. The ₁-adrenergic receptor component (that is not evident in wild-type cells) stimulates glucose uptake through a PI3K and PKC pathway in the ₃-KO cells.