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

Abstract
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.
AuthorsJ Yamada, Y Sugimoto, T Yoshikawa, K Horisaka
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 323 Issue 2-3 Pg. 235-40 (Apr 04 1997) ISSN: 0014-2999 [Print] Netherlands
PMID9128844 (Publication Type: Journal Article)
Chemical References
  • Blood Glucose
  • Insulin
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • 5-Methoxytryptamine
  • Dexamethasone
  • Glucagon
Topics
  • 5-Methoxytryptamine (pharmacology)
  • Adrenal Medulla (physiology)
  • Animals
  • Blood Glucose (analysis)
  • Dexamethasone (pharmacology)
  • Glucagon (blood)
  • Insulin (blood)
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin (drug effects, physiology)
  • Serotonin Antagonists (pharmacology)
  • Serotonin Receptor Agonists (pharmacology)

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