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Direct and indirect actions of 5-hydroxytryptamine on the discharge of mesenteric afferent fibres innervating the rat jejunum

Authors


  • Author's present address

    K. Hillsley: Department of Anatomy and Neurobiology, C-423 Given Building, University of Vermont, Burlington, VT 05405, USA.

Corresponding authors D. Grundy: Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK. Email: d.grundy@sheffield.ac.uk

Abstract

  • 1This study was performed to elucidate the actions of 5-hydroxytryptamine (5-HT) on mesenteric afferent discharge and to determine the receptor-mechanisms responsible for these effects. The activity of mesenteric afferents innervating the mid-jejunum of urethane-anaesthetized rats was recorded with extracellular microelectrodes. The discharge of single nerves within the whole nerve recording was monitored using waveform discriminator software.
  • 2The intravenous injection of 5-HT produced a complex pattern of afferent activation with two distinct components which could be distinguished both in terms of the response characteristics and the receptors involved. Initially, in 64 % of nerve bundles, there was a brief (2.0 ± 0.1 s) but intense activation of afferent discharge with peak afferent firing increasing with incremental doses of 5-HT. The discharge frequency in seventeen single units from these bundles during the initial response to 10 μg 5-HT was 13.0 ± 1.8 impulses s−1 from a baseline discharge of 1.0 ± 0.1 impulses s−1.
  • 3This initial response was mimicked by the 5-HT3 receptor agonist, 2-methyl-5-HT, whereas 5-methoxytryptamine (5-MEOT, 10–100 μg) had no comparable effect. Similarly, the initial 5-HT response was completely abolished by the 5-HT3 receptor antagonist, granisetron (0.5 mg kg−1).
  • 45-HT also evoked, in approximately 35 % of nerve bundles, a delayed response that single unit analysis showed to be mediated by an entirely different population of afferents from those activated during the initial response. This secondary response to 5-HT was characterized by a more prolonged (> 30 s) but less intense period of afferent activity which was coincident with an increase in intrajejunal pressure, and was mimicked by 5-MEOT (10–100 μg).
  • 5The secondary response to 5-HT and the response to 5-MEOT were significantly attenuated by the 5-HT2A receptor antagonist, ketanserin (0.5 mg kg−1), which had no effect on the initial response.
  • 6The initial response to 5-HT was unaffected by the L-type calcium channel inhibitor nifedipine (1 mg kg−1) or the N-type calcium channel inhibitor ω-conotoxin GVIA (25 μg kg−1). However, the secondary response to 5-HT was significantly reduced after treatment with nifedipine.
  • 7These results demonstrate that 5-HT activates different populations of afferent fibres innervating the rat jejunum. One population of afferents is activated directly via stimulation of 5-HT3 receptors, while another population responds to 5-HT with a time course consistent with secondary activation of mechanosensitive afferents following 5-HT2A-mediated contractile activity.

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