Influence of 5-ht1 and 5-ht2 receptor antagonists on insulin-induced adrenomedullary catecholamine release

Francis Chaouloff*, Sue H. Gunn, James B. Young

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Previous works have indicated that insulin stress activates the serotonin (5-HT) and sympathoadrenal systems in the fasted rat. In addition, recent studies have shown that activation of either the 5-ΗΤ1A, the 5-HT1C or the 5-HT2 receptor triggers adrenal catecholamine release. Then, the aim of this study was to investigate whether brain 5-HT, by means of these receptors, mediates insulin-induced adrenal catecholamine release. For that purpose, both plasma epinephrine (Epi), norepinephrine (NE) and glucose levels were measured in conscious rats bearing intracardiac catheters. The intravenous administration of insulin (1 IU/kg) triggered hypoglycemia throughout the following 120 min in both fed and overnight fasted rats. Insulin stress elicited within 30 min a 5- and 38-fold increase in plasma Epi levels in fed and fasted rats, respectively. This change was associated with significant elevations in plasma NE levels in the fasted rats only. The intravenous administration of the mixed 5-HT1A receptor/β-adrenoceptor blocker (−)-propranolol (5 mg/kg) to fasted rats did not modify plasma glucose and catecholamine peak responses to insulin; however, at later times, insulin triggered hypoglycemic convulsions in (−)-propranolol- but not in saline-pretreated rats. Besides, pretreatments with the 5-HT1C/5-HT2 receptor blocker LY 53857 (0.5 mg/kg), or the 5-HT1/5-HT2 receptor antagonist metergoline (3 mg/kg), did not diminish plasma catecholamine responses to insulin stress. Similarly, none of these antagonists affected plasma glucose recovery. These results seem to indicate that the sympathoadrenal response to insulin administration is not mediated by 5-HT.

Original languageEnglish (US)
Pages (from-to)639-645
Number of pages7
JournalNeuroendocrinology
Volume54
Issue number6
DOIs
StatePublished - 1991

Keywords

  • 5-HT receptors
  • Glucose
  • Insulin administration
  • Plasma catecholamines
  • Sympathoadrenal system

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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