Tachykinin receptors in gastrointestinal motility

Holzer‐Petsche, Ulrike

doi:10.1016/0167-0115(95)00019-8

Cited by 51 publications

(26 citation statements)

References 194 publications

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“…Substance P has at least two sites of action in guinea pig ileum, NK1 receptor on the longitudinal smooth muscles and NK 3 receptor on cholinergic nerves causing release of acetylcholine (16,26). When substance P is released from intrinsic nerves, substance P stimulates NK1 receptor on the longitudinal smooth muscles and induces contraction even with an inhibition of muscarinic receptors.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Atropine-Resistant Contraction Induced by Dai-kenchu-to in Guinea Pig Ileum

Satoh

Hashimoto

Hayakawa

et al. 2001

Japanese Journal of Pharmacology

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ABSTRACT-To clarify the contractile mechanism of Dai-kenchu-to, the effects of hydroxy b -sanshool (an ingredient of Zanthoxylum fruit), Zanthoxylum fruit (a constituent herb of Dai-kenchu-to) and Daikenchu-to were studied in mucosa-free longitudinal muscle of guinea pig ileum. Hydroxy b -sanshool at 10 -7 -10 -5 g/ ml induced dose-related contractions accompanied by autonomous contraction and produced an initial contraction at a concentration of 10 -4 g/ml or more. The contraction induced by hydroxy b -sanshool (10 -5 g/ ml) was significantly inhibited by tetrodotoxin or the capsaicin-receptor antagonist capsazepine. Although atropine or the substance P antagonist spantide tended to inhibit the contraction, a combination of atropine and spantide almost abolished the contraction by hydroxy b-sanshool. The P2-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid did not affect hydroxy b-sanshool-induced contraction in the presence or absence of spantide. The tonic contractions by Zanthoxylum fruit (2´10 -4 g/ml) and Dai-kenchu-to (10 -3 g/ml) were significantly inhibited or tended to be inhibited by atropine, spantide, tetrodotoxin or capsazepine and were remarkably suppressed by the combination of atropine and spantide. These results suggested that acetylcholine release from intrinsic cholinergic nerves and tachykinins from sensory neurons are involved in the contractions induced by hydroxy b-sanshool and that tachykinins may be involved in the atropine-resistant contraction by Dai-kenchu-to.Keywords: Dai-kenchu-to, Zanthoxylum fruit, Hydroxy b-sanshool, Intestinal motility, Tachykinin Dai-kenchu-to (Da-Jian-Zhong-Tang in Chinese) is a traditional Chinese herbal medicine, called Kampo medicine in Japan, and is a mixture of Zanthoxylum fruit, ginseng, dried ginger root and malt sugar. This formula is known for clinical effects on intestinal obstruction subsequent to laparotomy (1, 2). In vivo studies have demonstrated that Dai-kenchu-to enhanced gastrointestinal motility in dogs and rabbits (2, 3), and prevented intestinal adhesion in rats (4). In experiments using isolated intestines, Daikenchu-to induced contractions in rabbit jejunum, guinea pig ileum and colon, and relaxed guinea pig gastric body (5 -8). These reports indicated that Zanthoxylum fruit induces contraction; however, the other constituent herbs had no significant contractile effect on the isolated intestine. In guinea pig ileum and colon, contractions due to Dai-kenchu-to and Zanthoxylum fruit are mediated by acetylcholine release from the ends of cholinergic nerves, and 5-HT4 receptors are involved (7,8). In addition, since we also noted that a mucosa-free preparation resists the contractile response to atropine (8), it was suggested that other neurotransmitters are involved in the contractile effect of Dai-kenchu-to.Hydroxy b-sanshool is considered to be one of the active compounds involved in inducing contraction by Zanthoxylum fruit (9, 10). It was reported that the contractile effect is due to the release of acetylch...

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Section: Discussionmentioning

confidence: 99%

Mechanism of Atropine-Resistant Contraction Induced by Dai-kenchu-to in Guinea Pig Ileum

Satoh

Hashimoto

Hayakawa

et al. 2001

Japanese Journal of Pharmacology

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“…Substance P (SP) and neurokinin A (NKA), two members of muscle induced by SP and NKA is mediated by NK, (SPthe tachykinin family of peptides, fulfil the criteria required for preferring) and NK2 (NKA-preferring) receptors (see Bartho them to be considered as excitatory transmitters to the circular & Holzer, 1985;Holzer-Petsche, 1995 (see Maggi et al, 1993 for review): these tools enable precise assessment of the role of endogenous tachykinins as enteric neurotransmitters and of different ta-'Author for correspondence at: Pharmacology Department, chykinin receptors in these events (e.g. Bartho et al, 1992; Menarini Ricerche, Via Sette Santi 3, 50131, Florence, Italy.…”

Section: Introductionmentioning

confidence: 99%

Evidence that tachykinin NK₂ receptors modulate resting tone in the rat isolated small intestine

Maggi

Giuliani

1996

British J Pharmacology

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1 In the progress of experiments aimed at evaluating the role of tachykinins as enteric nonadrenergic noncholinergic (NANC) transmitters, we noted that certain tachykinin receptor antagonists produce a relaxation of circular muscle strips in the rat small intestine. This study aimed to assess the nature of this response and to determine the receptor type involved. The majority of the experiments were performed in capsaicin-(10 gM for 15 min) pretreated mucosa-free circular muscle strips from the rat small intestine, in the presence of atropine (1 gM), guanethidine (3 gM) and indomethacin (10 gM).2 Under isometric recording of mechanical activity, the tachykinin NK1 receptor antagonist SR 140,333 (0.1 gM) had no effect on resting tone or spontaneous activity in duodenal or ileal circular muscle strips. The NK2 receptor antagonists, MEN 10,627 (0.1 gM) and GR 94,800 (0.1 gM) produced, after a delay of 10-15 min, a relaxation which averaged 61+3 and 57 + 6% (n= 6 and 4, respectively) of the maximal response (E,) to isoprenaline (1 gM). The effect of maximal concentrations of MEN 10,627 and GR 94,800 when applied together was non-additive. The relaxant effect of MEN 10,627 (0.1 gM) was similar in the absence and presence of apamin (0.3 gM) and L-nitroarginine (100 gM). (1 gM) and GR 82,334 (10 gM) were also without effect (n=4-5). 5 A cocktail of peptidase inhibitors, thiorphan, bestatin and captopril (1 gM each) had no significant effect on tone or spontaneous activity of duodenal strips. In the presence of peptidase inhibitors, MEN 10,627 (1 gM) produced a relaxation of duodenal strips (72+6% of E,,m,, to isoprenaline, n=5), whilst GR 82,334 (10 gM, n = 6) had no significant effect.6 The relaxant response to MEN 10,627 was preserved in mucosa-free strips not pre-exposed to capsaicin. Tetrodotoxin (1 gM), saxitoxin (1 gM), hexamethonium (100 gM) and cw-conotoxin (0.1 MM) had no significant effect on the resting tone of duodenal strips nor did they affect the relaxation to MEN 10,627. L-Nitroarginine (100 Mm) increased the tone of the strips but did not affect the response to MEN 10,627. Nifedipine (1 gM) relaxed the strips by 62+4% (n = 4), but in its presence a small relaxant effect to MEN 10,627 (26 + 5%, n = 4) was still evident.7 Under isotonic recording of mechanical activity along the longitudinal axis, MEN 10,627 (1 MM) produced a slowly developing relaxation (39 + 3% of Em,,, to isoprenaline; n = 6) of whole segments of rat duodenum. When similar experiments were performed on whole segments of rat proximal colon MEN 10,627 had no effect.8 The present findings document the observation that tachykinin NK2 receptors contribute to the maintenance of resting tone of the rat isolated small intestine. We found no evidence to suggest that this effect follows the blockade of the contractile effect of spontaneously released endogenous tachykinins.The present findings raise the possibility that constitutively active NK2 receptors account for the relaxant effect produced by NK2 receptor antagonists in rat small intesti...

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“…The most investigated action of tachykinins in the gut relates to their role as neuromuscular excitatory transmitters which involves the activation of either NK1 (SP-preferring) or NK2 (NKA-preferring) tachykinin receptors (for reviews see Barth6 and Holzer 1985;Holzer-Petsche 1995 andShuttleworth andKeef 1995).…”

Section: Introductionmentioning

confidence: 99%

In vivo evidence for the involvement of tachykinin NK3 receptors in the hexamethonium-resistant inhibitory transmission in the rat colon

Lecci

Giuliani

Tramontana

et al. 1996

Naunyn-Schmiedeberg's Arch Pharmacol

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In urethane-anaesthetized rats, moderate colonic distention (0.5 ml) induced reflex rhythmic contractions (5 mm Hg amplitude and 1.1 cycles/min frequency). Senktide (1-10 nmol/kg, i.v.), a tachykinin NK3 receptor selective agonist, transiently suppressed distension-induced contractions. SR 142,801 (1-10 mumol/kg i.v.), a non-peptide tachykinin NK3 receptor antagonist, had no effect on distension-induced contractions but prevented the inhibitory effect of senktide. Infusion of N-omega-nitro-1-arginine methyl esther hydrochloride (L-NAME, 20 mumol/ml/h, i.v) increased the amplitude of colonic contractions and decreased the inhibitory effect of senktide. Hexamethonium (15 mumol/ml/h, i.v.) or atropine (1 mumol/ml/h, i.v.) inhibited the distension-induced contractions. In hexamethonium- or atropine-treated rats, senktide (10 nmol/kg) transiently and selectively enhanced the amplitude of contractions. Also SR 142,801 (10 mumol/kg), but not its inactive enantiomer SR 142,806, increased both amplitude and frequency of contractions. During continuous infusion of L-NAME and hexamethonium or atropine both frequency and amplitude of distension-induced colonic contractions were higher than when in hexamethonium or atropine only. Senktide (10 nmol/kg) had no effect and SR 142,801 (10 mumol/kg) produced a slight enhancement of colonic contractions. Infusion of sodium nitroprusside (3 mumol/ml/h, i.v.) decreased amplitude and frequency of distension-induced contractions. SR 142,801 had no effect in the presence of the nitric oxide (NO) donor. We conclude that tachykinins acting through NK3 receptors exert at least four different actions on colonic motility activated by distension: 1) a hexamethonium-resistant, NO-dependent, suppressant effect on contractions; 2) a hexamethonium-sensitive, NO-independent inhibitory effect on the amplitude of contractions; 3) a hexamethonium-resistant, NO-independent inhibitory effect on the amplitude of contractions and 4) a hexamethonium resistant and L-NAME-sensitive excitatory effect on amplitude of contractions. The prevalent inhibitory effect evoked in normal conditions along with the excitatory activity induced by SR 142,801 on hexamethonium-resistant colonic motility indicates that tachykinins, acting through neuronal NK3 receptors, activate NO-dependent and NO-independent inhibitory neurotransmission in the rat colon.

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Tachykinin receptors in gastrointestinal motility

Cited by 51 publications

References 194 publications

Mechanism of Atropine-Resistant Contraction Induced by Dai-kenchu-to in Guinea Pig Ileum

Mechanism of Atropine-Resistant Contraction Induced by Dai-kenchu-to in Guinea Pig Ileum

Evidence that tachykinin NK₂ receptors modulate resting tone in the rat isolated small intestine

In vivo evidence for the involvement of tachykinin NK3 receptors in the hexamethonium-resistant inhibitory transmission in the rat colon

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Tachykinin receptors in gastrointestinal motility

Cited by 51 publications

References 194 publications

Mechanism of Atropine-Resistant Contraction Induced by Dai-kenchu-to in Guinea Pig Ileum

Mechanism of Atropine-Resistant Contraction Induced by Dai-kenchu-to in Guinea Pig Ileum

Evidence that tachykinin NK2 receptors modulate resting tone in the rat isolated small intestine

In vivo evidence for the involvement of tachykinin NK3 receptors in the hexamethonium-resistant inhibitory transmission in the rat colon

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Evidence that tachykinin NK₂ receptors modulate resting tone in the rat isolated small intestine