Lipolytic Action ofButhus occitanus tunetanusVenom: Involvement of the β Adrenergic Pathway

Abstract

Scorpion venoms contain active neurotoxins known to act selectively at the level of voltage sensitive Na+and K+channels on mammal nervous system. In the present report, we show for the first time that the venom of scorpionButhus occitanus tunetanus(Bot) countains compounds able to activate another cell function in non excitable cells. Addition of this venom to the culture media of 3T3-L1 adipocytes or freshly dissociated rat adipocytes rapidly increases lipolysis as estimated by glycerol release (∼3 to 4 fold over basal values) in a dose-dependent manner (EC50∼12 ± 1.25 μg/ml; n=3). Bot venom effect was lower and not additive to the effect produced by isoproterenol (IPE) (10 μM), a main lipolytic agent, n=3. In Sephadex G-50 size exclusion chromatography, the lipolytic activity was excluded and not associated to the included neurotoxic fraction. Furthermore, no lipolytic effect could be detected in the Na+channel specific toxin II purified fromAndroctonus australis hector(AaHII) or the K+voltage-dependent channel toxin fromAndroctonus mauritanicus mauritanicus(KTx). Propranolol (a non selective β adrenoreceptor (βAR) antagonist), alprenolol and pindolol (selective β1/β2 antagonists) totally inhibited in a dose-dependent manner the lipolytic response to Bot venom (IC50∼1×10−7, 7.5×10−8and 3×10−7M, respectively), suggesting that venom stimulated lipolysis through the β AR pathway. The pharmacological profiles of molecules acting more selectively on β AR subtypes such as CGP 12177 (β1/β2 antagonist with β3 agonist properties), CGP 20712A (β1 antagonist) and ICI 118551 (β2 antagonist) strongly suggest that lipolytic action of venom mainly involves the β2/β1 AR subtypes.