title: B(2) kinin receptors mediate the Indian red scorpion venom-induced augmentation of visceral reflexes via the nitric oxide cyclic guanosine monophosphate pathway.
abstract: OBJECTIVE
  This study was performed to delineate the kinin (receptor)-dependent pathways in the Indian red scorpion (Mesobuthus tamulus; MBT) venom-induced pulmonary oedema as well as the augmentation of cardio-pulmonary reflexes evoked by phenyldiguanide (PDG).
  
  
  METHODS
  In urethane-anaesthetized adult rats, the effect of venom on the PDG reflex responses (blood pressure, heart rate and respiration rate) and the pulmonary water content was ascertained using various antagonists(des- Arg, B(1) receptor antagonist; Hoe 140, B(2) receptor antagonist; N(omega)-nitro-l-arginine methyl ester (l-NAME), nitric oxide (NO) synthase inhibitor; methylene blue, soluble guanylate cyclase inhibitor; and glibenclamide, K(+)(ATP) channel blocker). The effect of phosphodiesterase V inhibitor (sildenafil citrate) on the reflex response and the pulmonary water content was also examined and compared with venom-induced responses.
  
  
  RESULTS
  Intravenous injection of PDG (10 microg kg(-1)) evoked apnoea, bradycardia and hypotension lasting >60 s. Exposure to MBT venom (100 microg kg(-1)) for 30 min augmented the PDG reflex responses by two times and increased the pulmonary water content, significantly. Hoe 140 blocked the venom-induced responses (augmentation of PDG reflex and increased pulmonary water content) whereas des-Arg did not. l-NAME, methylene blue or glibenclamide also blocked the venom-induced responses. Furthermore, sildenafil citrate (that increases cGMP levels) produced augmentation of PDG reflex response and increased the pulmonary water content as seen with venom.
  
  
  CONCLUSIONS
  The results indicate that venom-induced responses involve B(2) kinin receptors via the NO-dependent guanylate cyclase-cGMP pathway involving K(+)(ATP) channels.
authors.affiliation: Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, Uttar Pradesh, India.
authors.forename: S
authors.initials: S
authors.lastname: Kanoo
authors.forename: A B
authors.initials: AB
authors.lastname: Alex
authors.forename: A K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: S B
authors.initials: SB
authors.lastname: Deshpande
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001645:Biguanides / Q000008:administration & dosage / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006157:Guanosine Monophosphate / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D011687:Purines / Q000494:pharmacology; D051381:Rats; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects*; D012604:Scorpion Venoms / Q000494:pharmacology*; D012605:Scorpions; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000378:metabolism; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D001645:Biguanides; D065094:Bradykinin B2 Receptor Antagonists; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D010879:Piperazines; D011687:Purines; D043782:Receptor, Bradykinin B2; D012604:Scorpion Venoms; D017366:Serotonin Receptor Agonists; D013450:Sulfones; D009569:Nitric Oxide; C065679:icatibant; D006157:Guanosine Monophosphate; D000068677:Sildenafil Citrate; D001920:Bradykinin; D005905:Glyburide; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester; C008846:phenyl biguanide