CARDIOVASCULAR EFFECTS OF MASTOPARAN-B AND ITS STRUCTURAL REQUIREMENTS

Mastoparan B is a cationic, amphiphilic tetradecapeptide (LKLKSIVSWAKK VL-CONH2,) isolated from the venom of the hornet Vespa basalis. Intrav enous injection of the peptide into rats caused a profound depression of blood pressure and cardiac function, which was inhibited by cyprohe ptadine, reserpine and multiple doses of compound 48/80, but not by di phenhydramine and cromolyn. Mastoparan from Paravespula lewisii showed little cardiovascular inhibitory activity. A synthetic mastoparan B a nalog in which lysine at position 2 was replaced by asparagine showed a marked decrease in the cardiovascular depressor effects, while repla cing lysine at position 4, 11 or 12 with leucine did not cause a signi ficant reduction in these effects. Replacing lysine at position 12 wit h leucine even caused a more sustained depressor effect. However, the analog in which lysines at positions 11 and 12 were replaced by leucin e lost its cardiovascular inhibitory activity. Replacing tryptophan at position 9 with phenylalanine in mastoparan B did not affect its acti vity. It is concluded that mastoparan B is involved in the cardiovascu lar disturbances induced by the hornet venom. Lysine at position 2 is a critical residue for the cardiovascular effects of mastoparan B. A p eptide molecule with two lysine residues, one located close to the ami no terminus and the other near the carboxyl end of the peptide, appear s to be the optimal structure for eliciting the cardiovascular depress or effects.