The bee venom phospholipase A(2) (PLA(2)) inhibitory activity of petrosaspongiolide M (PM), a marine metabolite displaying a potent anti-inflammatory activity and able to covalently bind and block group II and III secretory PLA(2) enzymes, has been investigated by mass spectrometry and molecular modeling. The model reveals interesting insight on the PM-PLA(2) inhibition process and may prove useful in the design of new anti-inflammatory agents targeting PLA(2) secretory enzymes. In this paper, the effect of PM has been investigated on opiate withdrawal in an in vitro model. After a 4 min in vitro exposure to morphine a strong contracture of guinea pig isolated ileum was observed after the addition of naloxone. PM treatment 1 x 10(-8), 5 x 10(-8), 1 x 10(-7) M was able to reduce morphine withdrawal. These results suggest that PM effect in this in vitro model of opiate withdrawal may be due to extracellular type II PLA(2) inhibition.

Petrosaspongiolide M Reduces Morphine Withdrawal in Vitro

RANDAZZO, ANTONIO;
2003

Abstract

The bee venom phospholipase A(2) (PLA(2)) inhibitory activity of petrosaspongiolide M (PM), a marine metabolite displaying a potent anti-inflammatory activity and able to covalently bind and block group II and III secretory PLA(2) enzymes, has been investigated by mass spectrometry and molecular modeling. The model reveals interesting insight on the PM-PLA(2) inhibition process and may prove useful in the design of new anti-inflammatory agents targeting PLA(2) secretory enzymes. In this paper, the effect of PM has been investigated on opiate withdrawal in an in vitro model. After a 4 min in vitro exposure to morphine a strong contracture of guinea pig isolated ileum was observed after the addition of naloxone. PM treatment 1 x 10(-8), 5 x 10(-8), 1 x 10(-7) M was able to reduce morphine withdrawal. These results suggest that PM effect in this in vitro model of opiate withdrawal may be due to extracellular type II PLA(2) inhibition.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/205502
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