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Role of 5-HT3 receptors in activation of abdominal sympathetic C fibre afferents during ischaemia in cats

Authors

  • Liang-Wu Fu,

    1. Division of Cardiovascular Medicine, Departments of Internal Medicine and Human Physiology, University of California School of Medicine, Davis, CA 95616, USA
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  • John C. Longhurst

    1. Division of Cardiovascular Medicine, Departments of Internal Medicine and Human Physiology, University of California School of Medicine, Davis, CA 95616, USA
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Corresponding author L.-W. Fu: Division of Cardiovascular Medicine, TB 172, University of California at Davis, Davis, CA 95616, USA. Email: lwfu@ucdavis.edu

Abstract

  • 1Activation of abdominal sympathetic afferents during ischaemia reflexly excites the cardiovascular system. We have shown previously that exogenous 5-hydroxytryptamine (5-HT, i.e. serotonin) stimulates abdominal sympathetic afferent nerve endings, and recently have documented increased concentrations of 5-HT in intestinal lymph and portal venous plasma during brief abdominal ischaemia. The present investigation evaluated the role of endogenously produced 5-HT in activation of ischaemically sensitive abdominal sympathetic afferents.
  • 2Nerve activity of single-unit C fibre afferents innervating duodenum, mesentery, pancreas, portal hepatis, bile duct, gall bladder and jejunum was recorded from the right thoracic sympathetic chain of anaesthetized cats. Ischaemically sensitive C fibre afferents were identified according to their response to 5-10 min of abdominal ischaemia.
  • 3Intra-arterial injection of 5-HT (20 μg kg−1) increased discharge activity of twelve afferents from 0.23 ± 0.05 to 0.96 ± 0.09 impulses s−1 after an onset latency of 5.7 ± 1.4 s. Also, 2-methylserotonin (100 μg kg−1, i.a.), a 5-HT3 receptor agonist, stimulated eleven of twelve afferents to significantly increase their discharge activity from 0.25 ± 0.05 to 0.90 ± 0.10 impulses s−1 after a latency of 3.3 ± 0.4 s. Furthermore, intravenous injection of tropisetron (200 μg kg−1), a 5-HT3 receptor antagonist, significantly attenuated the increase in activity of twelve other C fibre afferents during 10 min of abdominal ischaemia from 1.62 ± 0.18 to 0.94 ± 0.22 impulses s−1, and eliminated the response of eleven other afferents to 5-HT.
  • 4Both the 5-HT2 receptor agonist, α-methylserotonin (100 μg kg−1, i.a.), and the 5-HT1 receptor agonist, 5-carboxamidotryptamine (100 μg kg−1, i.a.), did not alter the impulse activity of these twelve afferents (0.29 ± 0.05 to 0.31 ± 0.06, and 0.26 ± 0.06 to 0.29 ± 0.06 impulses s−1, respectively).
  • 5Treatment with indomethacin (5 mg kg−1, i.v.) in eight different cats did not alter the response of nine C fibre afferents to exogenous 5-HT (0.91 ± 0.17 vs. 1.19 ± 0.25 impulses s−1, P > 0.05).
  • 6The results suggest that, during mesenteric ischaemia, endogenous 5-HT contributes to the activation of abdominal sympathetic afferents, mainly through direct stimulation of 5-HT3 receptors and that the action of 5-HT on these afferents appears to be independent of the cyclo-oxygenase pathway.

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