title: Involvement of NO-guanylyl cyclase pathway for the depression of spinal monosynaptic reflex by Mesobuthus tamulus venom in neonatal rat in vitro.
abstract: OBJECTIVE
  The present study was undertaken to evaluate the role of nitric oxide (NO) in Mesobuthus tamulus (MBT) venom-induced depression of spinal reflexes.
  
  
  METHODS
  Experiments were performed on isolated hemisected spinal cords from 4 to 6day old rats. Stimulation of a dorsal root with supramaximal strength evoked monosynaptic (MSR) and polysynaptic reflex (PSR) potentials in the corresponding segmental ventral root.
  
  
  RESULTS
  Superfusion of MBT venom (0.3μg/ml) depressed the spinal reflexes in a time-dependent manner and the maximum depression was seen at 10min (MSR by 63%; PSR by 79%). The time to produce 50% depression (T-50) of MSR and PSR was 7.7±1.3 and 5.7±0.5min, respectively. Pretreatment with bicuculline (1μM; GABA(A) receptor antagonist) or strychnine (1μM; glycine(A) receptor antagonist) did not block the venom-induced depression of spinal reflexes. However, Nω-nitro-L-arginine methyl ester (L-NAME, 100 or 300μM; NO synthase inhibitor) or hemoglobin (Hb, 100μM; NO scavenger) antagonized the venom-induced depression of MSR. Further, soluble guanylyl cylase inhibitors (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one, ODQ; 1μM or methylene blue, 100μM) also antagonized the venom-induced depression of MSR but not PSR. Nitrite concentration (indicator of NO activity) of the cords exposed to venom (0.3μg/ml) was not different from the control group.
  
  
  CONCLUSIONS
  The results indicate that venom-induced depression of MSR is mediated via NO-guanylyl cyclase pathway without involving GABAergic or glycinergic system.
authors: Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India.
authors: Amar N
authors: AN
authors: Maurya
authors: Shripad B
authors: SB
authors: Deshpande
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D012023:Reflex, Monosynaptic / Q000187:drug effects / Q000502:physiology*; D012604:Scorpion Venoms / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D012604:Scorpion Venoms; D009569:Nitric Oxide; D006162:Guanylate Cyclase