Monoamine oxidase inhibitory activities of the scorpion Mesobuthus gibbosus (Buthidae) venom peptides.
In the present study, crude venom of Mesobuthus gibbosus (Buthidae), a scorpion distributed all over Anatolia was isolated and purified by the Sephadex G-50 gel filtration and high pressure liquid chromatographic (HPLC) separation. Two of the five fractions (fractions 4 and 5) obtained from the Sephadex G-50 filtration and detected as lethal on mice and Musca domestica larvae in in vivo toxicity tests, were independently subjected to the HPLC separation. Only one of seven fractions (fraction 5.5*) obtained from the HPLC separation of the fraction 5 was found to be extremely lethal. Sodium dodecylsulfate polyacrylamide gel electrophoretic (SDS-PAGE) analysis of the crude venom and its chromatographic fractions demonstrated that crude venom consisted of peptides with molecular weights of 6500-210,000 Da. The neurotoxic fraction 5.5* appeared as a single band of 28,000 Da and two bands of 6200 and 22,000 Da in SDS-PAGE under non-reducing and reducing conditions, respectively, suggesting that it might consist of two chains attached by a disulfide bridge. Fractions 5 and 5.5* inhibited monoamine oxidase A (MAO-A) of rat liver reversibly and non-competitively, in a concentration-dependent manner. Fraction 5.5* appeared as a potent and specific MAO-A inhibitor with a Ki value of 0.12 mg venom proteinml(-1). The inhibitory effect of venom peptide 5.5* on MAO-A was found to be dependent on the preincubation time suggesting that the peptide binds to some site other than the substrate-binding site. Results of the present study demonstrated that M. gibbosus venom contains a peptide with specific MAO-A inhibitory activity which may be responsible for the anxiogenic effects of the scorpion venoms on animals and humans.
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Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey. gulberk@hacettepe.edu.tr
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D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D006793:Houseflies / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D007814:Larva / Q000187:drug effects; D008099:Liver / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D010455:Peptides; D012604:Scorpion Venoms