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

J Auton Pharmacol. 1998 Oct;18(5):313-7. doi: 10.1046/j.1365-2680.1998.185100.x.

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 micromol kg(-1) i.v.) or the histamine H1-receptor antagonist, diphenhydramine (34.5 micromol 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 micromol kg(-1) i.v., respectively. 3. The tachykinin NK-2 or NK-3 receptor agonists [beta-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 microM. The selective tachykinin NK-2 receptor agonist ([beta-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.

MeSH terms

  • Animals
  • Dipeptides / pharmacology
  • Diphenhydramine / pharmacology
  • Dose-Response Relationship, Drug
  • Esophagogastric Junction / drug effects
  • Evans Blue / pharmacokinetics
  • Extravasation of Diagnostic and Therapeutic Materials*
  • Guinea Pigs
  • Indoles / pharmacology
  • Inflammation / physiopathology*
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Neurokinin-1 Receptor Antagonists
  • Peptides, Cyclic / pharmacology*
  • Receptors, Neurokinin-1 / agonists
  • Receptors, Neurokinin-2 / agonists
  • Receptors, Neurokinin-2 / antagonists & inhibitors
  • Receptors, Neurokinin-3 / agonists
  • Receptors, Neurokinin-3 / antagonists & inhibitors*
  • Receptors, Tachykinin* / classification
  • Receptors, Tachykinin* / physiology
  • Substance P / analogs & derivatives*
  • Substance P / pharmacology*

Substances

  • Dipeptides
  • Indoles
  • Neurokinin-1 Receptor Antagonists
  • Peptides, Cyclic
  • Receptors, Neurokinin-1
  • Receptors, Neurokinin-2
  • Receptors, Neurokinin-3
  • Receptors, Tachykinin
  • substance P, Sar(9)-Met(O2)(11)-
  • FK 888
  • MEN 10627
  • Substance P
  • Evans Blue
  • Diphenhydramine