Lipolytic action of Buthus occitanus tunetanus venom: involvement of the beta adrenergic pathway

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) contains 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 (approximately 3 to 4 fold over basal values) in a dose-dependent manner (EC50 approximately 12 +/- 1.25 micrograms/ml; n = 3). Bot venom effect was lower and not additive to the effect produced by isoproterenol (IPE) (10 microM), 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 beta adrenoreceptor (beta AR) antagonist), alprenolol and pindolol (selective beta 1/beta 2 antagonists) totally inhibited in a dose-dependent manner the lipolytic response to Bot venom (IC50 approximately 1 x 10(-7), 7.5 x 10(-8) and 3 x 10(-7)M, respectively), suggesting that venom stimulated lipolysis through the beta AR pathway. The pharmacological profiles of molecules acting more selectively on beta AR subtypes such as CGP 12177 (beta 1/ beta 2 antagonist with beta 3 agonist properties), CGP 20712A (beta 1 antagonist) and ICI 118551 (beta 2 antagonist) strongly suggest that lipolytic action of venom mainly involves the beta 2/beta 1 AR subtypes.