Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 379, Issue 5, pp 525–532

Cardiac dysrhythmia produced by Mesobuthus tamulus venom involves NO-dependent G-Cyclase signaling pathway

  • Sadhana Kanoo
  • Maloy B. Mandal
  • Anitha B. Alex
  • Shripad B. Deshpande
Original Article

Abstract

Role of G-protein coupled pathways in modulating the cardiotoxic effects produced by Indian red scorpion (Mesobuthus tamulus) venom were examined. The isometric contractions of spontaneously beating or paced (3.5 Hz) rat right atrial preparations in vitro were recorded. The cumulative concentration (0.01–3.0 μg/ml)-response of venom on spontaneously beating atria exhibited a marked decrease in rate (by 55%) and an increase in force (by 92%) only at a higher concentration (3.0 μg/ml). The venom-induced decrease in rate and increase in force were sensitive to atropine, N-ω-nitro-l-arginine methylester (NO synthase inhibitor) and methylene blue (guanylyl cyclase inhibitor). Further, nifedipine, a Ca2+ channel antagonist, blocked the force changes but not the rate changes induced by venom. In the paced atrium, on the other hand, a concentration-dependent decrease in force was observed, and at 3 μg/ml, the decrease was 50%. Pretreatment with nifedipine, but not with methylene blue, significantly attenuated the venom-induced force changes in paced atrium. The observations of this study demonstrate that the venom-induced atrial dysrhythmia is mediated through the muscarinic receptor-dependent NO-G-cyclase cell-signaling pathways.

Keywords

c-GMP Guanylyl cyclase Indian red scorpion venom l-NAME Methylene blue Nifedipine 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Sadhana Kanoo
    • 1
  • Maloy B. Mandal
    • 1
  • Anitha B. Alex
    • 1
  • Shripad B. Deshpande
    • 1
  1. 1.Department of Physiology, Institute of Medical SciencesBanaras Hindu UniversityVaranasiIndia

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