Inflammatory and motor responses by tachykinins in the guinea-pig oesophageal sphincter

Authors: Conte B.; Parlani M.; Lopez G.; Cirillo R.; Maggi C.A.; Manzini S.

Source: Journal of Autonomic Pharmacology, Volume 18, Number 5, October 1998 , pp. 313-318(0)

Publisher: Wiley-Blackwell

Abstract:

1 The aim of this study was to characterize the tachykinin receptors involved in producing plasma protein extravasation and contractile responses of the guinea-pig oesophageal sphincter.

2 In anaesthetized guinea-pigs, the selective tachykinin NK-1 receptor agonist [Sar⁹,Met(O₂)¹¹]substance P produced plasma protein extravasation (PPE) which was not affected by the treatment with the tachykinin NK-2 receptor antagonist MEN 10627 (1 mol kg^--1 i.v.) or the histamine H₁-receptor antagonist, diphenhydramine (34.5 mol kg^--1 i.v.). However, the [Sar⁹,Met(O₂)¹¹]substance P-induced PPE was blocked by the previous administration of the peptide tachykinin NK-1 receptor antagonist FK 888 or by the non-peptide antagonist SR 140333, yielding ED₅₀ values of 1.1 ± 0.2 and 0.01 ± 0.004 mol kg^--1 i.v., respectively.

3 The tachykinin NK-2 or NK-3 receptor agonists [-Ala⁸]neurokinin A (4–10) or [MePhe⁷]neurokinin B, respectively, produced a weak PPE at high doses. The effect of [MePhe⁷]neurokinin B-induced PPE was inhibited by SR 140333.

4 In the guinea-pig isolated oesophageal sphincter, [Sar⁹,Met(O₂)¹¹]substance P did not exert any contractile effect up to 10 m. The selective tachykinin NK-2 receptor agonist ([-Ala⁸]neurokinin A (4–10), produced concentration-dependent contractions (pD₂ = 7.6 ± 0.03) which were inhibited by the selective tachykinin NK-2 receptor antagonist, MEN 10627 (pA₂ = 8.6 ± 0.1). Also, the tachykinin NK-3 receptor selective agonist [MePhe⁷]neurokinin B induced concentration-dependent contractile responses, but these responses were inhibited by MEN 10627.

5 Altogether, these data indicate that the stimulation of tachykinin NK-1 receptor produces a vascular inflammatory response, while activation of tachykinin NK-2 receptors mediate the contraction of the guinea-pig oesophageal sphincter.

Language: English

Document Type: Research article

Publication date: 1998-10-01

• In this: publication
• By this: publisher
• In this Subject: Pharmacology
• By this author: Conte B. ;  Parlani M. ;  Lopez G. ;  Cirillo R. ;  Maggi C.A. ;  Manzini S.

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