Tachykininergic transmission to the circular muscle of the guinea-pig ileum

Evidence for the involvement of NK2 receptors

L. Barthó, P. Santicioli, R. Patacchini, C. A. Maggi

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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 μM) and apamin (0.1 μM) evoked a complex motor response. The tonic primary contraction in this response was reduced by GR 71,251 (10 μM) and MEN 10,376 (3-10 μM) but not by L 659,877 (up to 10 μM). 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 μM) inhibited the tonic contraction produced by [Sar9] substance P sulphone, a selective NK1 receptor agonist but not that produced by [β Ala8] 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 NK1 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 atropine-sensitive phasic contractions (ascending enteric reflex). In the presence of atropine (2 μM), 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 μM) and abolished by tetrodotoxin, either in the presence of absence of apamin. 5. MEN 10,376 (3-10 μM) inhibited the atropine-resistant ascending enteric reflex in the presence of apamin while GR 71,251 or L 659,877 (10 μM 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.

Original languageEnglish
Pages (from-to)805-810
Number of pages6
JournalBritish Journal of Pharmacology
Volume105
Issue number4
Publication statusPublished - 1992

Fingerprint

Atropine
Ileum
Apamin
Guinea Pigs
Muscles
cyclo(Gln-Trp-Phe-Gly-Leu-Met)
Reflex
Tachykinin Receptors
Tetrodotoxin
Tachykinins
Sulfones
Substance P
Cholinergic Agents
Electric Stimulation
Tyr(5)-Trp(6,8,9)-Lys(10)-neurokinin A(4-10)
GR 71251

Keywords

  • Ascending enteric reflex
  • Circular muscle
  • Guinea-pig ileum
  • Tachykinin receptors
  • Tachykinins

ASJC Scopus subject areas

  • Pharmacology

Cite this

Tachykininergic transmission to the circular muscle of the guinea-pig ileum : Evidence for the involvement of NK2 receptors. / Barthó, L.; Santicioli, P.; Patacchini, R.; Maggi, C. A.

In: British Journal of Pharmacology, Vol. 105, No. 4, 1992, p. 805-810.

Research output: Contribution to journalArticle

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