title: Cardiac dysrhythmia produced by Mesobuthus tamulus venom involves NO-dependent G-Cyclase signaling pathway.
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 microg/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 microg/ml). The venom-induced decrease in rate and increase in force were sensitive to atropine, N-omega-nitro-L-arginine methylester (NO synthase inhibitor) and methylene blue (guanylyl cyclase inhibitor). Further, nifedipine, a Ca(2+) 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 microg/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.
authors.affiliation: Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221 005, India.
authors.forename: Sadhana
authors.initials: S
authors.lastname: Kanoo
authors.forename: Maloy B
authors.initials: MB
authors.lastname: Mandal
authors.forename: Anitha B
authors.initials: AB
authors.lastname: Alex
authors.forename: Shripad B
authors.initials: SB
authors.lastname: Deshpande
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000201:enzymology; D006152:Cyclic GMP / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism*; D006325:Heart Atria / Q000187:drug effects* / Q000201:enzymology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012604:Scorpion Venoms / Q000633:toxicity*; D012605:Scorpions; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D012604:Scorpion Venoms; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester