Tachykinin receptors in the circular muscle of the guinea‐pig ileum

Maggi, Carlo Alberto; Patacchini, Riccardo; Giachetti, Antonio; Meli, Alberto

doi:10.1111/j.1476-5381.1990.tb14195.x

Cited by 76 publications

(60 citation statements)

References 28 publications

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“…In spite of being important for under standing the genesis of propulsive activity and peristalsis, analysis of receptors responsible for tachykinin actions in the circular muscle has not been performed until recently. By using strip preparations of guinea pig ileal circular muscle, Maggi et al (11) and Bartho et al (12) We found, as is to be shown in the present study, that SP had much more capability to induce contractions in the circular muscle of guinea pig ileum in segment prepa rations than in strip preparations.…”

supporting

confidence: 69%

Tachykinin-Induced Contractions in the Circular Muscle of Guinea Pig Ileum.

Suzuki¹,

Muramatsu²,

Gomi³

1994

Jpn.J.Pharmacol

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ABSTRACT-Actions of substance P (SP, 10-9 to 10-6 M), neurokinin A (NKA, 10-9 to 10-6 M) and neurokinin B (NKB, 10-10 to 10-6 M) in the circular muscle of guinea pig ileum were investigated in segment and strip preparations, in which methacholine produced similar contractions. In the segment preparations, three tachykinins produced repeatedly occurring twitch-like contractions. Their efficacies were similar with the same maximal contractions, but their potencies were different (NKB > NKA = SP). Latency (38 sec) was observed before the initiation of contractions in response to NKA, but not to SP or NKB. Atropine (10-6 M) and tetrodotoxin (3 x 10-'M) did not affect NKA-induced contractions, but inhibited SP and NKB induced contractions; the dose-response curves for SP and NKB were rightwardly shifted by atropine. The treatment with atropine brought out latency in the responses for NKB. In the strip preparations, SP did not substantially induce contractions, but NKA and NKB produced twitch-like contractions after latent periods of 28 and 36 sec, respectively. The efficacy of NKA was similar to that in segment preparations, while that of NKB was much lower in strip preparations. Unlike in segment preparations, atropine did not inhibit contrac tions induced by the two tachykinins in strip preparations. These results suggest that tachykinins induce con tractions through myogenic and neurogenic mechanisms, the latter of which may be inoperative in strip preparations.

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supporting

confidence: 69%

Tachykinin-Induced Contractions in the Circular Muscle of Guinea Pig Ileum.

Suzuki¹,

Muramatsu²,

Gomi³

1994

Jpn.J.Pharmacol

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“…By use of natural TKs and receptor-selective TK agonists, evidence has been presented that NKI, NK2 and NK3 receptors mediate the spasmogenic action of TKs in the circular Author for correspondence. muscle of the guinea-pig ileum (Maggi et al, 1990a); the response to NK2 receptor stimulation seems to be entirely ascribable to direct smooth muscle activation, that produced by NK3 receptor stimulation is entirely neurogenic while that produced by NK1 receptor stimulation has intermediate char-…”

Section: Introductionmentioning

confidence: 99%

Tachykininergic transmission to the circular muscle of the guinea‐pig ileum: evidence for the involvement of NK₂ receptors

Barthó

Santicioli

Patacchini

et al. 1992

British J Pharmacology

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1 The effect of newly developed, receptor-selective tachykinin antagonists (GR 71,251 for NK1 receptors, MEN 10,376 and L 659,877 for NK2 receptors) on noncholinergic transmission to the circular muscle of the guinea-pig ileum has been investigated. 2 In circular muscle strips of the ileum, electrical field stimulation in the presence of atropine (2 jM) and apamin (0.1 jAM) evoked a complex motor response. The tonic primary contraction in this response was reduced by GR 71,251 (10 jM) and MEN 10,376 (3-10 I1M) but not by L 659,877 (up to 10 jM). The presence of apamin was necessary in this experimental arrangement to unmask an atropine-resistant primary contraction, sensitive to tachykinin antagonists. The motor response was abolished by tetrodotoxin.3 In circular strips of the ileum GR 71,251 (10 jM) inhibited the tonic contraction produced by [Sar9] substance P sulphone, a selective NK1 receptor agonist but not that produced by [,B Alal] neurokinin A (4-10), a selective NK2 receptor agonist. By contrast, MEN 10,376 antagonized the effect of the NK2 agonist while leaving the response to the NK, agonist unaffected. 4 In whole segments of the ileum, distension of the gut wall by an intraluminal balloon placed at about 1 cm from the point of recording of mechanical activity of the circular muscle produced atropinesensitive phasic contractions (ascending enteric reflex). In the presence of atropine (2 jiM), a noncholinergic response was elicited, which required larger volumes of distension that the cholinergic one. The atropine-resistant ascending enteric reflex was enhanced by apamin (0.1 j1M) and abolished by tetrodotoxin, either in the presence or absence of apamin. 5 MEN 10,376 (3-lOM) inhibited the atropine-resistant ascending enteric reflex in the presence of apamin while GR 71,251 or L 659,877 (10 lM each) were ineffective. MEN 10,376 inhibited the atropine-resistant ascending enteric reflex to a larger extent in the absence than in the presence of apamin and also slightly inhibited the ascending enteric reflex in the absence of atropine. 6 These findings provide evidence for an involvement of NK2 tachykinin receptors in excitatory transmission to the circular muscle of the guinea-pig ileum. NK2 receptors are also involved in the physiological-like circular muscle activation produced by stimulation of intramural neuronal pathways which subserve the atropine-resistant ascending enteric reflex.

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“…In mammals, three peptides of this family, namely, sub stance P (SP), neurokinin (NK)-A and NK-B, are believed to play a role as neurotransmitters, either in the peripher al or the central nervous system (1). Tachykinins act as excitatory transmitters in the mammalian gut, where they exert potent spasmogenic effects via specific receptors, termed NK,, NK2 and NK3; and they are located on mus cle cells or indirectly generated by activating intramural neurons (2,3). In vitro studies showed that activation of NK2-receptors produces potent spasmogenic effects in several segments of the intestine (3,4).…”

mentioning

confidence: 99%

“…Tachykinins act as excitatory transmitters in the mammalian gut, where they exert potent spasmogenic effects via specific receptors, termed NK,, NK2 and NK3; and they are located on mus cle cells or indirectly generated by activating intramural neurons (2,3). In vitro studies showed that activation of NK2-receptors produces potent spasmogenic effects in several segments of the intestine (3,4). In the last few years, new selective and potent NK2-receptor antagonists have been discovered (1), allowing researchers to define the effect of tachykinins in various organs.…”

mentioning

confidence: 99%

Spasmolytic Effect of the NK2-Receptor-Selective Antagonist MEN 10,627 in Rat Small Intestine.

1994

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ABSTRACT-The effect of activation of tachykinin NK2-receptors on gastrointestinal propulsion was studied in vivo in conscious rats. The selective NK2-receptor agonist [j3A1a8]NKA-(4-10) produced an atro pine-resistant specific increase of the small intestinal transit measured by the charcoal method. This effect was restricted to the small intestine since gastric emptying was not affected by [ f3Ala8]NKA-(4-10). The new ly developed polycyclic peptide NK2-receptor antagonist MEN 10,627 produced a dose-dependent inhibition of this stimulated transit. The spasmolytic effect of MEN 10,627 was highly selective because it did not affect stimulated intestinal transit induced by equieffective doses of carbachol and reserpine. These findings in dicate that MEN 10,627 is a valuable tool for assessing the role of NK2-receptors in intestinal propulsive activity.

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Tachykinin receptors in the circular muscle of the guinea‐pig ileum

Cited by 76 publications

References 28 publications

Tachykinin-Induced Contractions in the Circular Muscle of Guinea Pig Ileum.

Tachykinin-Induced Contractions in the Circular Muscle of Guinea Pig Ileum.

Tachykininergic transmission to the circular muscle of the guinea‐pig ileum: evidence for the involvement of NK₂ receptors

Spasmolytic Effect of the NK2-Receptor-Selective Antagonist MEN 10,627 in Rat Small Intestine.

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Tachykinin receptors in the circular muscle of the guinea‐pig ileum

Cited by 76 publications

References 28 publications

Tachykinin-Induced Contractions in the Circular Muscle of Guinea Pig Ileum.

Tachykinin-Induced Contractions in the Circular Muscle of Guinea Pig Ileum.

Tachykininergic transmission to the circular muscle of the guinea‐pig ileum: evidence for the involvement of NK2 receptors

Spasmolytic Effect of the NK2-Receptor-Selective Antagonist MEN 10,627 in Rat Small Intestine.

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Tachykininergic transmission to the circular muscle of the guinea‐pig ileum: evidence for the involvement of NK₂ receptors