Indian red scorpion (Buthus tamulus) venom-induced augmentation of cardiac reflexes is mediated through the involvement of peripheral 5-HT3 and central 5-HT1A receptor subtypes.
The present study was undertaken to identify 5-HT receptor subtypes involved in Buthus tamulus (BT) venom-induced augmentation of cardiac reflexes elicited by phenyldiguanide (PDG). Intravenous injection of PDG (10 microg/kg) produced parallel decrease in mean arterial pressure (MAP) and heart rate (HR) in urethane anaesthetized rats (r=0.82; p < 0.001). Injection of PDG (1-40 microg/kg, i.v.) produced concentration-dependent decrease in time-response area of the HR. After BT venom (20 microg/kg) the concentration-response curve was shifted to the left. Further, fall of MAP and HR in response to submaximal concentration of PDG (10 microg/kg) were augmented significantly. Pretreatment with 5-HT3 receptor antagonist (ondansetron; 10 microg/kg) intravenously, blocked the BT venom-induced augmentation of PDG reflex but spiperone (100 microg/kg; 5-HT1A/5-HT2 antagonist) or ketanserin (300 microg/kg; 5-HT2 antagonist) failed to do so. Afferent discharges elicited by PDG (10 microg/kg) in vagus nerve were doubled after exposure to BT venom. Ondansetron (100 microg/kg, i.v.) totally abolished the discharges after exposure to BT venom but not by spiperone or ketanserin. Intracerebroventricular injection of spiperone (100 microg/kg) but not ketanserin or ondansetron, blocked the BT venom-induced augmentation of PDG reflex. Results show that the BT venom-induced augmentation of reflex elicited by PDG is mediated through the involvement of 5-HT3 receptors peripherally and 5-HT1A type of receptors centrally.
Bagchi
S
S
Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Deshpande
S B
SB
D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002490:Central Nervous System / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007650:Ketanserin / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D017933:Peripheral Nervous System / Q000378:metabolism; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D044406:Receptors, Serotonin, 5-HT3; D012018:Reflex / Q000502:physiology*; D012604:Scorpion Venoms / Q000494:pharmacology*; D012605:Scorpions; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013134:Spiperone / Q000008:administration & dosage / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*
D001645:Biguanides; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D044406:Receptors, Serotonin, 5-HT3; D012604:Scorpion Venoms; D017366:Serotonin Receptor Agonists; D017294:Ondansetron; D013134:Spiperone; D007650:Ketanserin; C008846:phenyl biguanide