European Journal of Pharmacology 1998-10-16

Effects of the non-selective 5-HT receptor agonist, 5-carboxamidotryptamine, on plasma glucose levels in rats.

J Yamada, Y Sugimoto, T Noma, T Yoshikawa

Index: Eur. J. Pharmacol. 359 , 81, (1998)

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Abstract

The effects of the 5-HT1A/1B/1D/5/7 receptor agonist, 5-carboxamidotryptamine (5-CT), on blood glucose, insulin and glucagon levels in rats were investigated. 5-CT above the dosage of 0.05 mg/kg elicited significant hyperglycemic effects and 0.1 mg/kg, induced a 35% increase in plasma glucose levels. 5-CT did not affect plasma glucagon, and serum insulin levels increased following the high dose of 5-CT. Adrenodemedullation abolished the 5-CT-induced hyperglycemia. Hyperglycemia induced by 5-CT was prevented by pretreatment with the 5-HT1/2/7 receptor antagonist, metergoline, and the 5-HT1/2/5/7 receptor antagonist, methysergide, although the 5-HT2A receptor antagonist, ketanserin, the 5-HT2A/2B/2C receptor antagonist, ritanserin, and the 5-HT3/4 receptor antagonist, tropisetron, had no effect. Although 5-CT has a high affinity with 5-HT1A receptors, the 5-HT1A and 5-HT1B and beta receptor antagonist, (-)-popranolol, did not affect 5-CT-induced hyperglycemia. These results indicate that 5-CT-induced hyperglycemia is elicited by facilitation of adrenaline release from the adrenal gland and that 5-CT-induced hyperglycemia is mediated by the 5-HT7 receptor unrelated to 5-HT1A, 5-HT1B, 5-HT2, 5-HT3, 5-HT4 or 5-HT5 receptors.