Hyperglycemia induced by the 5-HT receptor agonist, 5-methoxytryptamine, in rats: involvement of the peripheral 5-HT2A receptor

The effects of the 5-HT Receptor Agonist, 5-methoxytryptamine, on plasma glucose levels were investigated in rats. 5-Methoxytryptamine induced a significant hyperglycemia above the dosage of 1 mg/kg. 5-Methoxytryptamine-induced hyperglycemia was antagonized by pretreatment with the 5-HT1 and 5-HT2 receptor antagonist, methysergide, or the 5-HT2A receptor antagonist, ketanserin, whereas the 5-HT3 and 5-HT4 receptor antagonist, tropisetron, and the 5-HT4 receptor antagonist, SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino) ethyl ester), showed no effect. In addition, the peripheral 5-HT2 receptor antagonist, xylamidine, reduced 5-methoxytryptamine-induced hyperglycemia. These results suggest that 5-methoxytryptamine-induced hyperglycemia is mediated by the peripheral 5-HT2A receptor, although it has a high affinity for the 5-HT4 receptor. Adrenodemedullation abolished the 5-methoxytryptamine-induced hyperglycemia. 5-Methoxytryptamine did not affect the blood levels of the pancreatic Hormones, Insulin and glucagon. The hyperglycemia induced by 5-methoxytryptamine was not affected by pretreatment with dexamethasone which inhibits corticosterone release. These results indicate that 5-methoxytryptamine-induced hyperglycemia is elicited by a facilitated adrenaline release from the adrenal gland. Therefore, it is suggested that the 5-HT2A receptor may be partly involved in the pharmacological effects induced by the 5-HT4 receptor agonist, 5-methoxytryptamine.