Role of capsaicin-sensitive afferent neurons in alkaline secretory response to luminal acid in the rat duodenum

Takeuchi, Koji; Matsumoto, Jiro; Ueshima, Koji; Okabe, Susumu

doi:10.1016/0016-5085(91)90721-v

Cited by 109 publications

(105 citation statements)

References 24 publications

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“…Because this response is substantially inhibited by indomethacin, it is speculated that the afferent side of this reflex pathway is influenced by PGs, probably by facilitating the neuronal excitation in response to H ϩ . Indeed, we have previously reported that acid-induced HCO 3 Ϫ secretion was significantly attenuated by chemical ablation of capsaicin-sensitive afferent neurons and that the stimulatory action of capsaicin was also suppressed by indomethacin (12,19). It is assumed that local PGE 2 release stimulates the reflex pathway on the afferent side and may also directly stimulate the epithelial cells, both resulting in an increase in the secretion of HCO 3 Ϫ .…”

Section: Discussionmentioning

confidence: 99%

“…All capsaicin injections were performed under ether anesthesia, and the rats were pretreated with terbutaline (0.1 mg/kg im) and aminophylline (10 mg/kg im) to counteract the respiratory impairment associated with capsaicin injection. To check for the effectiveness of the treatment, a drop of capsaicin solution (0.1 mg/ml) was instilled into one eye of each rat, and wiping movements were counted as previously reported (19).…”

Section: Methodsmentioning

confidence: 99%

“…It is believed that the acid-induced HCO 3 Ϫ secretion is mediated via an axonal reflex pathway in addition to endogenous PGs (10,19). Because this response is substantially inhibited by indomethacin, it is assumed that endogenous PGE 2 also stimulates the reflex pathway on the afferent side, in addition to directly stimulating the epithelial cells, both resulting in an increase in HCO 3 Ϫ secretion.…”

Section: Effects Of Verapamil and Ibmx On Duodenal Hcomentioning

confidence: 99%

“…prostaglandin E2; EP receptor subtype; EP4 receptor SECRETION OF HCO 3 Ϫ FROM surface epithelial cells is one of the mucosal defensive mechanisms and plays an important role in protecting the duodenal mucosa against acid injury (6,4,18). Although the physiological regulation of this secretion involves several factors such as PGs, peptides, and neuronal factors (4,10,19,20), endogenous PGs are particularly important in the local control of the process. We (23) previously investigated the relationship between PGE receptor (EP) subtypes and HCO 3 Ϫ secretion, using specific EP1, EP2, and EP3 agonists, and found that the secretion was stimulated by EP agonists having a potent affinity for EP3 receptors.…”

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confidence: 99%

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Participation of prostaglandin E receptor EP4 subtype in duodenal bicarbonate secretion in rats

Aoi

Aihara

Nakashima

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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We examined, by using a specific PGE receptor subtype EP4 agonist and antagonist, the involvement of EP4 receptors in duodenal HCO 3 Ϫ secretion induced by PGE2 and mucosal acidification in rats. Mucosal acidification was achieved by exposing a duodenal loop to 10 mM HCl for 10 min, and various EP agonists were given intravenously 10 min before the acidification. Secretion of HCO 3 Ϫ was dose-dependently stimulated by AE1-329 (EP4 agonist), the maximal response being equivalent to that induced by sulprostone (EP1/EP3 agonist) or PGE2. The stimulatory action of AE1-329 and PGE2 but not sulprostone was attenuated by AE3-208, a specific EP4 antagonist. This antagonist also significantly mitigated the acidinduced HCO 3 Ϫ secretion. Coadministration of sulprostone and AE1-329 caused a greater secretory response than either agent alone. IBMX potentiated the stimulatory action of both sulprostone and AE1-329, whereas verapamil mitigated the effect of sulprostone but not AE1-329. Chemical ablation of capsaicin-sensitive afferent neurons did not affect the response to any of the EP agonists used. We conclude that EP4 receptors are involved in the duodenal HCO 3 Ϫ response induced by PGE2 or acidification in addition to EP3 receptors. The process by which HCO 3 Ϫ is secreted through these receptors differs regarding secondmessenger coupling. Stimulation through EP4 receptors is mediated by cAMP, whereas that through EP3 receptors is regulated by both cAMP and Ca 2ϩ ; yet there is cooperation between the actions mediated by these two receptors. The neuronal reflex pathway is not involved in stimulatory actions of these prostanoids. prostaglandin E2; EP receptor subtype; EP4 receptor SECRETION OF HCO 3 Ϫ FROM surface epithelial cells is one of the mucosal defensive mechanisms and plays an important role in protecting the duodenal mucosa against acid injury (6,4,18). Although the physiological regulation of this secretion involves several factors such as PGs, peptides, and neuronal factors (4,10,19,20), endogenous PGs are particularly important in the local control of the process. We (23) previously investigated the relationship between PGE receptor (EP) subtypes and HCO 3 Ϫ secretion, using specific EP1, EP2, and EP3 agonists, and found that the secretion was stimulated by EP agonists having a potent affinity for EP3 receptors. Using EP3 receptor knockout mice, we (21) also demonstrated the involvement of EP3 receptors in the acid-induced secretion of HCO 3 Ϫ in the duodenum. At that time, however, the possibility remained that the stimulatory action of PGE 2 is mediated by EP4 receptors, because specific EP4 agonists and antagonists were not available. It is now known that the increase in duodenal HCO 3 Ϫ secretion is mediated by the stimulation of adenylate cyclase (AC) activity and an elevation in intracellular cAMP levels (8,16,20) and that the activation of EP4 receptors results in an increase of intracellular cAMP via G s protein (3). Thus it is possible that EP4 receptors play a role in the regulation of duodenal HCO...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Effects Of Verapamil and Ibmx On Duodenal Hcomentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Participation of prostaglandin E receptor EP4 subtype in duodenal bicarbonate secretion in rats

Aoi

Aihara

Nakashima

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…It has been shown that capsaicin-sensitive afferents expressing TRPV1 play an important role in the transmission of the duodenal sensory information to the central nervous system when the duodenum is distended or perfused with acid (Holzer and Raybould 1992;Takeuchi et al 1991;Kagawa et al 2003). It is believed that low volume DD activates capsaicin-sensitive vagal afferents, whereas high volume DD involves splanchnic capsaicin-sensitive afferent fibers (Holzer and Raybould 1992).…”

Section: Afferent Pathwaysmentioning

confidence: 99%

Characterization of T9–T10 spinal neurons with duodenal input and modulation by gastric electrical stimulation in rats

et al. 2007

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Gastric electrical stimulation (GES) has been suggested as a therapy for patients with gastric motility disorders or morbid obesity. However, it is unclear whether GES also affects intestinal sensory and motor functions. Furthermore, little is known about intraspinal visceroreceptive transmission and processing for duodenal afferent information. The aims of this study were to characterize responses of thoracic spinal neurons to duodenal distension, to determine the afferent pathway, and to examine the effects of GES on activity of these neurons. Extracellular potentials of single T9-T10 spinal neurons were recorded in pentobarbital anesthetized, paralyzed, ventilated male rats (n=19). Graded duodenal distension (DD, 0.2-0.6 ml, 20 s) was produced by water inflation of a latex balloon surgically placed into the duodenum. One pair of platinum electrodes (1.0-1.5 cm apart) was sutured onto the serosal surface of the lesser curvature of the stomach. GES with four sets of parameters was applied for one minute: GES-A (6 mA, 0.3 ms, 40 Hz, 2s on, 3s off), GES-B (6 mA, 0.3 ms, 14 Hz, 0.1s on, 5s off), GES-C (6 mA, 3 ms, 40 Hz, 2s on, 3s off), GES-D (6 mA, 200 ms, 12 pulses/min). Results showed that 33/117 (28%) spinal neurons responded to noxious DD (0.4 ml, 20s). Of these, 7 (6%) neurons had low-threshold responses to DD (≤0.2 ml) and 26 (22%) had high-threshold responses to DD (≥0.4 ml). DD-responsive spinal neurons were encountered more frequently in deeper (depth: 0.3-1.2 mm) than in superficial laminae (depth: <0.3 mm) of the dorsal horn (24/67 vs 9/50, P<0.05). DD excited all 9 superficial neurons. In contrast, 20 deeper neurons were excited and 4 neurons were inhibited by DD. Activity of DD-responsive neurons was affected more frequently with GES-C (13/15, 87%) than GES-A (6/16, 38%), -B (3/15, 20%), -D (5/14, 36%), (P<0.01). Bilateral cervical vagotomy did not significantly alter the effects of DD and GES on 5/5 neurons. Resiniferatoxin (2.0 μg/kg, i.v.), an ultrapotent agonist of transient receptor potential vanilloid receptor-1 (TRPV1), abolished DD responses and GES effects on all neurons examined in vagotomized rats. Additionally, 29/33 (88%) DD-responsive neurons received inputs from somatic receptive fields on the back, flank, and medial/lateral abdominal areas. It was concluded that GES mainly exerted an excitatory effect on T9-T10 spinal neurons with duodenal input transmitted by sympathetic afferent fibers expressing TRPV1; spinal neuronal responses to GES were strengthened with an increased pulse width and/or frequency of stimulation; T9-T10 spinal neurons processed input from the duodenum and might mediate effects of GES on duodenal sensation and motility.

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Neuropeptides and the gut: Tachykinins and calcitonin gene-related peptide in intestinal inflammation and pain

Holzer

1999

Pain and Neurogenic Inflammation

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Role of capsaicin-sensitive afferent neurons in alkaline secretory response to luminal acid in the rat duodenum

Cited by 109 publications

References 24 publications

Participation of prostaglandin E receptor EP4 subtype in duodenal bicarbonate secretion in rats

Participation of prostaglandin E receptor EP4 subtype in duodenal bicarbonate secretion in rats

Characterization of T9–T10 spinal neurons with duodenal input and modulation by gastric electrical stimulation in rats

Neuropeptides and the gut: Tachykinins and calcitonin gene-related peptide in intestinal inflammation and pain

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