AhV_aPA-induced vasoconstriction involves the IP3Rs-mediated Ca2+ releasing

Abstract AhV_aPA, the acidic PLA 2 purified from Agkistrodon halys pallas venom, was previously reported to possess a strong enzymatic activity and can remarkably induce a further contractile response on the 60 mM K + -induced contraction with an EC 50 in 369 nM on mouse thoracic aorta rings. In the present study, we found that the p -bromo-phenacyl-bromide ( p BPB), which can completely inhibit the enzymatic activity of AhV_aPA, did not significantly reduce the contractile response on vessel rings induced by AhV_aPA, indicating that the vasoconstrictor effects of AhV_aPA are independent of the enzymatic activity. The inhibitor experiments showed that the contractile response induced by AhV_aPA is mainly attributed to the Ca 2+ releasing from Ca 2+ store, especially sarcoplasmic reticulum (SR). Detailed studies showed that the Ca 2+ release from SR is related to the activation of inositol trisphosphate receptors (IP 3 Rs) rather than ryanodine receptors (RyRs). Furthermore, the vasoconstrictor effect could be strongly reduced by pre-incubation with heparin, indicating that the basic amino acid residues on the surface of AhV_aPA may be involved in the interaction between AhV_aPA and the molecular receptors. These findings offer new insights into the functions of snake PLA 2 and provide a novel pathogenesis of A. halys pallas venom.