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 scorpion Buthus 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 (EC 50 ∼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 from Androctonus australis hector (AaHII) or the K + voltage-dependent channel toxin from Androctonus 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 (IC 50 ∼1×10 −7 , 7.5×10 −8 and 3×10 −7 M, 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.