Mast cell mediators excite the afferents of cat small intestine

Akoev, G. N.; Филиппова, Л В; Sherman, N. O.

doi:10.1016/0306-4522(95)00479-3

Cited by 23 publications

(10 citation statements)

References 14 publications

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“…The secondary response to 5‐HT occurred following a longer latency, usually after the initial response had subsided, and was characterized by a prolonged burst of firing that was coincident with an increase in intestinal pressure. Other groups have demonstrated intestinal afferent sensitivity to 5‐HT which follows a similar delayed time course (Lew & Longhurst, 1986; Akoev, Filippova & Sherman, 1996) but in the present study we have been able to demonstrate using waveform discrimination of single afferent units that this response to 5‐HT is mediated by a different population of afferents from those showing the initial 5‐HT response. The pharmacological profile of the secondary response was also different.…”

Section: Discussionsupporting

confidence: 50%

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

Hillsley

Kirkup

Grundy

1998

The Journal of Physiology

133

104

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1. This 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 urethaneanaesthetized rats was recorded with extracellular microelectrodes. The discharge of single nerves within the whole nerve recording was monitored using waveform discriminator software. 2. The 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 ìg 5_HT was 13·0 ± 1·8 impulses s¢ from a baseline discharge of 1·0 ± 0·1 impulses s¢. 3. This initial response was mimicked by the 5_HT× receptor agonist, 2-methyl-5_HT, whereas 5_methoxytryptamine (5_MEOT, 10-100 ìg) had no comparable effect. Similarly, the initial 5_HT response was completely abolished by the 5_HT× receptor antagonist, granisetron (0·5 mg kg¢). 4. 5_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 ìg). 5. The 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¢), which had no effect on the initial response. 6. The initial response to 5_HT was unaffected by the L-type calcium channel inhibitor nifedipine (1 mg kg¢) or the N-type calcium channel inhibitor ù_conotoxin GVIA (25 ìg kg¢). However, the secondary response to 5_HT was significantly reduced after treatment with nifedipine. 7. These 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_HT× 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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Section: Discussionsupporting

confidence: 50%

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

Hillsley

Kirkup

Grundy

1998

The Journal of Physiology

133

104

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“…This may reflect the differential expression of receptors on intrinsic and extrinsic nerves. However, in the small intestine of the cat in vivo , histamine‐induced afferent discharge was attenuated by the H 2 antagonist cimetidine (Akoev et al 1996), although this response may have been secondary to motor responses triggered by high concentrations of histamine. Other studies have implicated the involvement of H 1 receptors in mediating the actions of endogenous histamine on ischaemically sensitive visceral afferents in the cat (Fu et al 1997) and the activation of mesenteric afferents in the rat (Kreis et al 1998).…”

Section: Discussionmentioning

confidence: 99%

Sensitization of visceral afferents to bradykinin in rat jejunum in vitro

Brunsden

Grundy

1999

The Journal of Physiology

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The gastrointestinal tract has an extensive intrinsic and extrinsic sensory innervation. Despite this, stimuli in the healthy gastrointestinal tract rarely reach the level of conscious perception. In contrast, sensations of abdominal discomfort and pain are common symptoms in patients with gastrointestinal disease. Symptoms include heartburn, chest pain, dyspepsia, bloating, abdominal cramps and feelings of incomplete rectal evacuation, all of which can arise in both organic (e.g. inflammatory) and functional disorders such as irritable bowel syndrome. Visceral afferent hypersensitivity is now a widely accepted mechanism which could explain many of these clinical symptoms associated with functional bowel disease and inflammatory diseases of the gut (Mayer & Raybould, 1990;Bueno et al. 1997). However, the mechanisms underlying peripheral sensitization of gastrointestinal afferents is poorly understood. Much of our understanding of the mechanisms of afferent sensitization and the modulation of painful stimuli has stemmed from studies of cutaneous pain. Sensitization of cutaneous nociceptors is thought to underlie conditions of hyperalgesia (enhanced perception of pain) and allodynia where previously non-noxious stimuli can produce pain (Heller et al. 1993). Despite the lack of detailed studies on gastrointestinal afferent sensitivity, it is generally assumed that intestinal afferents behave in a similar way, being activated andÏor sensitized by chemical mediators present within an 'inflammatory soup'. Gastrointestinal afferents terminate at different levels within the gut wall (namely

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“…Activation of blood platelets is another possible source of increased serotonin concentrations in the inflamed tissue (Hranilovic et al , 1996; Marcenac & Blache, 1985). It is known that histamine enhances oedema formation mainly through the activation of H 1 and H 2 receptors (Akoev et al , 1996; Schwartz et al , 1991), and that serotonin induces plasma extravasation through 5‐HT 1 ‐ and 5‐HT 3 ‐receptor activation (Richardson, 1990; Taiwo & Levine, 1992). In the present study the bilateral oedema formation was blocked by 5‐HT 2 and 5‐HT 3 but not by histamine H 1 and 5‐HT 1 receptor antagonists.…”

Section: Discussionmentioning

confidence: 99%

“…It may be suggested that following the degranulation of mast cells and/or activation of blood platelets the proinflammatory substances are released. Thereafter, due to a close anatomical relationship between the mast cells and sensory nerves (Alving et al , 1991; Renda et al , 1992), there is an activation of nociceptive primary afferents (Akoev et al , 1996; Herbert & Schmidt, 1992) which triggers the release of neuropeptides, including CGRP, contributing to oedema formation (Maggi, 1995). Compared to SP, the capacity of CGRP in the activation of mast cells is less pronounced (Nilsson et al , 1990), most likely explaining why a dose of CGRP ten times lower (30 pmol, Newbold & Brain, 1993) than presently used did not induce hindpaw oedema formation.…”

Section: Discussionmentioning

confidence: 99%

Unilateral injection of calcitonin gene‐related peptide (CGRP) induces bilateral oedema formation and release of CGRP‐like immunoreactivity in the rat hindpaw

Bileviciute

Stenfors

Theodorsson³

et al. 1998

British J Pharmacology

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1 The contribution of calcitonin gene-related peptide (CGRP) to bilateral oedema formation in the rat hindpaw following an unilateral challenge with CGRP was investigated. 2 Rats were injected into the left hindpaw with either saline, CGRP or a CGRP antagonist (CGRP 8 ± 37 ). All injections were given in a double blind fashion and in a volume of 100 ml. CGRP and CGRP 8 ± 37 were administered in concentrations of 75, 150 or 300 pmol. Volumes of the right and left hindpaw were measured every hour for 5 h by plethysmometry. 3 Injection of CGRP 300 pmol into the left hindpaw resulted in a bilaterally increased hindpaw volume after 5 h as compared with the groups given saline. No changes were found in hindpaw volumes following the injection of either 75 or 150 pmol of CGRP or 75, 150 or 300 pmol of CGRP 8 ± 37 as compared with saline injection. 4 To elucidate whether or not the bilateral oedema formation was related to a release of endogenous CGRP, microdialysis of the contralateral hindpaw was carried out, and concentrations of CGRP-like immunoreactivity (-LI) were determined by radioimmunoassay and high performance liquid chromatography. Injection of CGRP 300 pmol into the left hindpaw increased the release of CGRP-LI into the right hindpaw perfusate after 4 and 5 h. No changes in CGRP-LI were detected in the right hindpaw perfusate following challenge with saline or CGRP 8 ± 37 . 5 To study the contribution of the nervous system to the contralateral release of CGRP-LI, sciatic nerve ligated and intact sham-operated rats were used. Sciatic nerve ligation but not sham-operation on the non-injected side abolished the increased release of CGRP-LI following contralateral administration of CGRP 300 pmol. 6 To study the spinal cord mechanisms resulting in the bilateral oedema formation following unilateral challenge with 300 pmol of CGRP, intrathecal pretreatment with either 10 nmol bicuculline (GABA A receptor antagonist) or 10 nmol CGRP 8 ± 37 was carried out. Bicuculline but not CGRP 8 ± 37 abolished the bilateral oedema formation induced by CGRP 300 pmol. 7 In order to study the mechanisms by which administration of CGRP 300 pmol induces oedema, CGRP 300 pmol was administered concomitantly with either 300 pmol of CGRP 8 ± 37 (CGRP receptor antagonist), or 3 nmol of promethazine (H 1 receptor antagonist), or 3 nmol of s(7)-propranolol (5-HT 1 receptor antagonist), or 3 nmol of cyproheptadine (5-HT 2 receptor antagonist) or 3 nmol of ICS 205 ± 930 (5-HT 3 receptor antagonist). Oedema formation was measured at 1, 5, 7 and 24 h. 8 Injection of CGRP 300 pmol into the left hindpaw induced a bilateral oedema formation which was still signi®cant at 24 h. Concomitant administration of either CGRP 8 ± 37 , ICS 205 ± 920 or cyproheptadine blocked the oedema formation at 24 h. No e ect on oedema formation was found when CGRP 300 pmol was co-administered with either promethazine or s(7)-propranolol (H 1 and 5-HT 1 receptor antagonists, respectively). 9 The results of the present study show that both the nervous system and local ...

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Mast cell mediators excite the afferents of cat small intestine

Cited by 23 publications

References 14 publications

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

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

Sensitization of visceral afferents to bradykinin in rat jejunum in vitro

Unilateral injection of calcitonin gene‐related peptide (CGRP) induces bilateral oedema formation and release of CGRP‐like immunoreactivity in the rat hindpaw

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