Release of slow reacting substance from the guinea-pig lung by phospholipases A2 of Vipera russelli snake venom.

Phospholipases A2 (PLA2) of Vipera russelli venom were isolated by column chromatography. The ability of PLA2 fractions to release slow reacting substance (SRS) was studied in the guinea-pig lung perfused with Krebs' solution. The relationship between the perfusion pressure change produced by PLA2 and SRS release was also studied. Two PLA2 fractions (II-5 and III-3; 3-100 micrograms), injected into the lung increased the perfusion pressure and released SRS. Pretreatment of the lung with indomethacin (10 micrograms) reduced the pressure response induced by the PLA2 fractions. The SRS released in the lung effluent by PLA2 was identified by bioassay as a mixture of thromboxane A2 (TXA2), prostacyclin (PGI2) and leukotrienes. TXA2 and PGI2 release was also quantitated by radioimmunoassay of the degradation products TXB2 and 6-keto-PGF1 alpha, respectively. There was a positive linear correlation between the pressure increases and the ratios of TXB2 to 6-keto-PGF1 alpha (r = 0.87). It appears that the relative amounts of TXA2 and PGI2 released determine the effects of PLA2 fractions on the guinea-pig lung. The release of arachidonic acid metabolites, prostaglandins and leukotrienes may account for part of the hypotensive action of PLA2.