The effects of crotapotin (a non-toxic and non-enzymatic acid polypeptide naturally complexed with phospholipase A(2)) and heparin on rat paw edema induced by different secretory,phospholipases A(2) (sPLA(2)) have been investigated. The ability of crotapotin to affect the enzymatic activity of the sPLA(2)(s) have also been evaluated. Secretory PLA(2)(s) obtained from both snake (Naja naja, Naja mocambique mocambique. Crotalus adamanteus and Crotalus durissus terrificus) and bee (Apis mellifera ) venoms as well as that from bovine pancreas were used in this study. Rat paw oedema was induced by a single subplantar injection of the sPLA(2)s (5-30 mu g/paw) in absence and presence of either crotapotin (10-100 mu g/paw) or heparin (50 U/paw), Paw volume was measured using a hydroplethysmometer. Phospholipase A(2) from Naja naja, Naja mocambique mocambique, Apis mellifera, n venoms and the basic component of Crotalus durissus terrificus venom all induced dose-dependent rat paw oedema whereas those from Crotalus adamanteus venom and bovine pancreas were ineffective. Paw oedema induced by PLA(2)(s) from both Naja naja and Apis mellifera venoms was significantly (P < 0.05) inhibited by crotapotin (0.1-100 mu g/site) whereas the Naja mocambique mocambique venom PLA(2)-induced oedema was significantly potentiated (P < 0.05) by this polypeptide (40 mu g/site). On the other hand, heparin (50 U/paw) had no effect on the paw oedema induced by PLA(2) from Naja naja and Apis mellifera venoms but significantly inhibited the Naja mocambique mocambique venom PLA(2)-induced oedema. The measurement of the in vitro phospholipasic activity revealed that crotapotin inhibited by 60-70% the enzymatic activities of PLA(2)(s) from Crotalus adamanteus, Naja mocambique mocambique, Apis mellifera venoms and bovine pancreas. Our results suggest that despite the great homology between the various types of sPLA(2) they interact with crotapotin on cell surfaces in different ways leading to either inhibition or potentiation of the paw oedema by a mechanism unrelated to their enzymatic activities. Since heparin reduced paw oedema induced by PLA(2) from Naja mocambique mocambique venom it is likely that this sPLA(2) is similar to the novel heparin-sensitive PLA(2) found in mast cells. (C) 1999 Elsevier Science Ltd. All rights reserved.382199208