Chromodacryorrhea and repetitive hind paw tapping: models of peripheral and central tachykinin NK1 receptor activation in gerbils

Eur J Pharmacol. 1994 Mar 3;253(3):245-52. doi: 10.1016/0014-2999(94)90198-8.

Abstract

The in vivo pharmacological profiles of the selective tachykinin NK1 receptor agonists, [Sar9,Met(O2)11]substance P and GR 73632, were examined in gerbils. Both agonists induced a pronounced chromodacryorrhea following intravenous injection which was stereoselectively antagonised by the tachykinin NK1 receptor antagonist, CP-99,994, but not by its inactive enantiomer, CP-100,263, or the rat-selective tachykinin NK1 receptor antagonist, RP 67,580. In contrast, chromodacryorrhea was not observed following intravenous injection of the selective tachykinin NK2 receptor agonist, [beta-Ala8]neurokinin A-(4-10), or the selective tachykinin NK3 receptor agonist, senktide. These results suggest that [Sar9,Met(O2)11]substance P-induced chromodacryorrhea results from activation of peripheral tachykinin NK1 receptors. Repetitive hind paw tapping was also observed in gerbils but only following intracerebroventricular injection of [Sar9,Met(O2)11]substance P or GR 73632. Furthermore, GR 73632-induced hind paw tapping was significantly attenuated by co-administration of the peptide tachykinin NK1 receptor antagonist, GR 82334, or intravenous injection of CP-99,994. Thus, in contrast to chromodacryorrhea, repetitive hind paw tapping may result from activation of central tachykinin NK1 receptors.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Gerbillinae
  • Harderian Gland / drug effects*
  • Harderian Gland / metabolism
  • Indoles / pharmacology
  • Injections, Intravenous
  • Injections, Intraventricular
  • Isoindoles
  • Male
  • Neurokinin A / antagonists & inhibitors
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology*
  • Piperidines / pharmacology
  • Receptors, Neurokinin-1 / drug effects*
  • Receptors, Neurokinin-1 / metabolism
  • Substance P / administration & dosage
  • Substance P / analogs & derivatives*
  • Substance P / antagonists & inhibitors
  • Substance P / pharmacology

Substances

  • Indoles
  • Isoindoles
  • Peptide Fragments
  • Piperidines
  • Receptors, Neurokinin-1
  • substance P, Sar(9)-Met(O2)(11)-
  • GR 73632
  • 7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one
  • 3-(2-methoxybenzylamino)-2-phenylpiperidine
  • Substance P
  • Neurokinin A