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AhV_aPA-induced vasoconstriction involves the IP₃Rs-mediated Ca²⁺ releasing
- Source :
- Toxicon : official journal of the International Society on Toxinology. 70
- Publication Year :
- 2012
-
Abstract
- AhV_aPA, the acidic PLA₂ 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 EC₅₀ in 369 nM on mouse thoracic aorta rings. In the present study, we found that the p-bromo-phenacyl-bromide (pBPB), 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 Ca²⁺ releasing from Ca²⁺ store, especially sarcoplasmic reticulum (SR). Detailed studies showed that the Ca²⁺ release from SR is related to the activation of inositol trisphosphate receptors (IP₃Rs) 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 PLA₂ and provide a novel pathogenesis of A. halys pallas venom.
- Subjects :
- Mice, Inbred ICR
Myocytes, Smooth Muscle
Acetophenones
Aorta, Thoracic
Ryanodine Receptor Calcium Release Channel
Mice
Phospholipases A2
Sarcoplasmic Reticulum
Vasoconstriction
Animals
Inositol 1,4,5-Trisphosphate Receptors
Vasoconstrictor Agents
Calcium
Agkistrodon
Muscle Contraction
Snake Venoms
Subjects
Details
- ISSN :
- 18793150
- Volume :
- 70
- Database :
- OpenAIRE
- Journal :
- Toxicon : official journal of the International Society on Toxinology
- Accession number :
- edsair.pmid..........6d644d0921c37f9c2e0697662aa94dac