Effects of octopamine on lipolysis, glucose transport and amine oxidation in mammalian fat cells.

Octopamine is known to exert adrenergic effects in mammals although specific octopamine receptors have been cloned only in invertebrates. It has been shown that octopamine can stimulate alpha(2)-adrenoceptors (ARs) in Chinese hamster ovary cells transfected with human alpha(2)-ARs. More recently, we reported that octopamine stimulates lipolysis through beta(3)-rather than beta(1)-or beta(2)-AR activation in white adipocytes from different mammalian species. The present study was thus undertaken to further characterize the adrenergic properties of octopamine. For this purpose, several biological processes known to be regulated by adrenergic stimulation were studied in response to octopamine, noradrenaline, adrenaline and tyramine in white adipocytes from different mammals. First, octopamine was fully lipolytic in garden dormouse and Siberian hamster while tyramine was ineffective. Although being around one hundred-fold less potent that noradrenaline, octopamine was slightly more potent in these hibernators known for their high sensitivity to beta(3)-AR agonists than in rat and chiefly more active than in human adipocytes known for their limited responses to beta(3)-AR agonists. Second, octopamine reduced insulin-dependent glucose transport in rat fat cells, a response also observed with noradrenaline and selective beta(3)-AR agonists but not with beta(1)-or beta(2)-agonists. Third, human adipocytes, which endogenously express a high level of alpha(2)-ARs, exhibited a clear alpha(2)-adrenergic antilipolytic response to adrenaline but not to octopamine. Moreover, octopamine exhibited only a very weak affinity for the alpha(2A)-ARs labeled by [3H]RX821002 in human adipocyte membranes. In Syrian hamster adipocytes, which also possess alpha(2)-ARs, octopamine induced only a weak antilipolysis. Finally, octopamine was a substrate of fat cell amine oxidases, with an apparent affinity similar to that of noradrenaline. All these results demonstrate that octopamine, tyramine noradrenaline and adrenaline can be degraded by adipocyte amine oxidases. However these biogenic amines interact differently with adipocyte adrenoceptors: tyramine is inactive, adrenaline and noradrenaline activate both beta- and alpha(2)-ARs while octopamine activates only beta(3)-ARs and is devoid of alpha(2)-adrenergic agonism. Thus, octopamine could be considered as an endogenous selective beta(3)-AR agonist.