Evidence that the contractile response of the guinea‐pig ileum to capsaicin is due to release of substance P.

Barthó, L.; Holzer, Peter; Lembeck, Fred; Szolcsányi, Janós

doi:10.1113/jphysiol.1982.sp014407

Cited by 114 publications

(42 citation statements)

References 42 publications

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“…Effects of capsaicin and SP on the cholinergic contraction by MN stimulation were substantially similar to those observed by other investigators (2,16,22) in all types of preparations, although the effects in bidirectional MN loops alone were significantly less intensive than in oral MN loops. Nevertheless, mean values of the percent response to each MN stimulation were distributed between 30 and 40% against that (10%) to oral MN stimulation.…”

Section: Discussionsupporting

confidence: 73%

INVOLVEMENT OF HEXAMETHONIUM-SENSITIVE AND CAPSAICIN-SENSITIVE COMPONENTS IN CHOLINERGIC CONTRACTIONS INDUCED BY MESENTERIC NERVE STIMULATION IN GUINEA-PIG ILEUM

Takaki¹,

Jin²,

Nakayama³

1987

Biomed. Res.

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Effects of hexamethonium (C6), capsaicin and substance P desensitization were tested on the cholinergic contraction in response to mesenteric nerve (MN) stimulation in four differently innervated loops of isolated guinea-pig ileum. Effect of oral MN stimulation was more intensive than that of anal MN stimulation in 80% of preparations innervated with both oral and anal mesenteric nerves. The result indicates that the innervation of oral MN is more dominant than that of anal MN.Moreover, overlap of the innervation of oral MN and anal MN was found. Response to oral MN stimulation or anal MN stimulation was unaffected by C6, but the response to bidirectional and oral-anal MN stimulation was significantly reduced to about 60 and 50% of the control, respectively. Effect of capsaicin or substance P desensitization on the response to each MN stimulation showed no marked differences among the four differently innervated loops. Szolcsanyi and Bartho (22) have postulated that the cholinergic contraction of the guineapig ileum to mesenteric periarterial nerve stimulation is mediated by the release of substance P (SP) from sensory nerve endings. This postulate is supported by observations that the cholinergic contraction by mesenteric nerve (MN) stimulation is abolished in an irreversible fashion by capsaicin which releases SP from primary sensory neurons (3, 14, 19), and that hexamethonium (C6) does not affect the cholinergic contraction at all (16, 22). Similar involvement of SP has been reported in the feline colon (12) and rat ileum (24). Vagal stimulation also causes hexamethonium-resistant contraction of the stomach, which might be attributed to antidromic activation of afferent fibres in cats (8, 10). It has been proposed that an SP-like peptide is involved in this response (9). However, the feline pylorus contraction induced by the vagal stimulation is abolished by C6 but persists after administration of atropine, indicating that cholinergic preganglionic fibres activate non-cholinergic excitatory neurones through nicotinic receptor (11, 20). Moreover, it has been reported that the mesenteric nerve contains a small proportion of vagal parasympathetic fibres in the rabbit (4, 13) and guinea-pig small intestine (17). Therefore, the aim of the present study is to reexamine whether the nicotinic transmission participates in the cholinergic contraction evoked by mesenteric nerve stimulation using four types of differently innervated preparations of guinea-pig small intestine. MATERIALS AND METHODSAdult guinea pigs of both sexes were stunned and exsanguinated. The ileum except its 20-cm long terminal portion was used for experiments. The segment of 2.5-cm or 3.0-cm long I

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Section: Discussionsupporting

confidence: 73%

INVOLVEMENT OF HEXAMETHONIUM-SENSITIVE AND CAPSAICIN-SENSITIVE COMPONENTS IN CHOLINERGIC CONTRACTIONS INDUCED BY MESENTERIC NERVE STIMULATION IN GUINEA-PIG ILEUM

Takaki¹,

Jin²,

Nakayama³

1987

Biomed. Res.

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“…26) Bartho et al reported that the contractile response of the guinea pig ileum to capsaicin was abolished by substance P antagonists (D-Pro2, D-Trp7, 9). 30) Naito et al also reported that plasma CGRP and substance P levels significantly increased after administration of Zingiberis rhizoma extract to healthy subjects. 31) Therefore these results suggest that hydroxyl b-sanshool and 6-shogaol are the predominant ingredients that stimulate CGRP and substance P release from nerve endings.…”

Section: )mentioning

confidence: 99%

Dai-kenchu-to Raises Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma

Sato

Katagiri

Inoue

et al. 2004

Biological & Pharmaceutical Bulletin

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Sensory afferent neurons in the gastrointestinal mucosa regulate neuropeptides [calcitonin gene-related peptide (CGRP), substance P, etc.], which play various physiologic roles and are gastroprotective. To determine whether the pharmacologic effects of Dai-kenchu-to (DKCT) on the gastrointestine are due to changes in gastrointestinal mucosa regulatory peptide levels, we examined the effects of the DKCT on the levels of CGRP-like immunoreactive substances (IS) and substance P-IS in plasma taken from five healthy subjects. A single oral administration of DKCT 7.5 g caused significant increases in plasma CGRP-IS at 40 min, and in substance P-IS levels at 20 and 60 min, compared with a placebo group. The present study may indicate that the pharmacologic action of DKCT is closely related to changes in CGRP-and substance P-IS levels.

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“…They also give rise to collaterals to myenteric and submucosal enteric ganglia, which largely lack mechanosensitivity 42 but which provide excitatory synaptic connections onto enteric neurons. [93][94][95] They also give rise to axon branches in the mucosa and muscle layers but do not have collaterals in either the serosal membranes or mesenteric membranes. For this reason, the names 'serosal' and 'mesenteric' are misleading.…”

Section: Type V: Spinal Vascular Afferentsmentioning

confidence: 99%

Extrinsic primary afferent signalling in the gut

Brookes

Spencer

Costa

et al. 2013

Nat Rev Gastroenterol Hepatol

246

216

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Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors, and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that there are just five structurally distinct types of sensory endings in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators.Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.2

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Evidence that the contractile response of the guinea‐pig ileum to capsaicin is due to release of substance P.

Cited by 114 publications

References 42 publications

<b>INVOLVEMENT OF HEXAMETHONIUM-SENSITIVE AND CAPSAICIN-SENSITIVE COMPONENTS IN CHOLINERGIC CONTRACTIONS INDUCED BY MESENTERIC NERVE STIMULATION IN GUINEA-PIG </b><b>ILEUM </b>

<b>INVOLVEMENT OF HEXAMETHONIUM-SENSITIVE AND CAPSAICIN-SENSITIVE COMPONENTS IN CHOLINERGIC CONTRACTIONS INDUCED BY MESENTERIC NERVE STIMULATION IN GUINEA-PIG </b><b>ILEUM </b>

Dai-kenchu-to Raises Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma

Extrinsic primary afferent signalling in the gut

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