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 mu g/kg) produced parallel decrease in mean arterial pressure (MAP) and heart rate (HR) in urethane anaesthetized rats (r = 0.52; p < 0.001), Injection of PDG (1-40 mu g/kg, i.v.) produced concentration-dependent decrease in time-response area of the IIR. After BT venom (20 mu g/kg) the concentration-response curve was shifted to the left. Further, fall of MAP and HR in response to submaximal concentration of PDG (10 mu g/kg) were augmented significantly. Pretreatment with 5-HT3 receptor antagonist (ondansetron; 10 mu g/kg) intravenously, blocked the BT venom-induced augmentation of PDG reflex but spiperone (100 mu g/kg; 5-HT1A/5-HT2 antagonist) or ketanserin (300 mu g/kg; 5-HT2 antagonist) failed to do so. Afferent discharges elicited by PDG (10 mu g/kg) in vagus nerve were doubled after exposure to BT venom. Ondansetron (100 mu g/kg, i.v.) totally abolished the discharges after exposure to BT venom but not by spiperone or ketanserin. Intracerebroventricular injection of spiperone (100 mu g/kg) but not ketanserin or ondansetron, blocked the BT venom-induced augmentation of PDG reflex. Results show that the BT venom-induced augmentation of rifler elicited by PDG is mediated through the involvement of 5-HT3 receptors peripherally and 5-HT1A type of receptors centrally. (C) 1999 Elsevier Science Ltd. All rights reserved.