Blocking properties of terguride at the 5-HT2 receptor subtypes mediating cardiovascular responses in the rat.
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY(2020)
摘要
In vitro studies have suggested that terguride blocks the contractile and relaxant responses produced by 5-hydroxytryptamine (5-HT) via 5-HT2A/2B receptors. This study has now investigated terguride's blocking properties on central/peripheral 5-HT2 receptors in anaesthetized or pithed rats. Male Wistar anaesthetized/pithed rats were cannulated for recording blood pressure and heart rate and for i.v. administration of several compounds. In both groups of rats, i.v. bolus injections of 5-HT or (+/-)-DO1 (a 5-HT2 receptor agonist; 1-1000 mu g/kg) produced dose-dependent increases in diastolic blood pressure and heart rate. These responses were dose-dependently antagonized by terguride (10-3000 mu g/kg). In anaesthetized rats, i.v. bolus injections of BW723C86 (a 5-HT28 receptor agonist; 1-1000 mu g/kg) produced dose-dependent increases in diastolic blood pressure and not dose-dependent increases in heart rate, while in pithed rats, these responses were attenuated. The vasopressor responses elicited by BW723C86 in anaesthetized rats were dose-dependently blocked by terguride (10-300 mu g(kg), whereas its the tachycardic responses were dose-independently blocked. These results, taken together, suggest that terguride behaved as an antagonist at the 5-HT2 receptors located in the central nervous system and (or) the systemic vasculature. This is the first evidence demonstrating that terguride can block central/peripheral 5-HT2 receptors mediating cardiovascular responses in anaesthetized or pithed rats.
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关键词
terguride,BW723C86,5-HT2 receptors,pithed rats,anaesthetized rats
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