Effects of tachykinins on phosphoinositide metaboism in the hypothalamus: is the NK1 receptor involved?

C. J. Lebrun, P. Wende, U. Steckelings, K. Itoi, Th Unger

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Substance P (SP) has been shown to stimulate the hydrolysis of inositol phospholipids in peripheral tissues and in the brain. In mammalian peripheral tissues, three tachykinin receptor subclasses, neurokinin 1 (NK1), neurokinin 2 (NK2) and neurokinin 3 (NK3), have been identified. The purpose of our study was to pharmacologically characterize the SP receptors in the hypothalamus using phosphoinositide breakdown as a functional response. SP, previously described as a NK1 agonist, and Neurokinin A (NKA), previously described as a NK2 agonist, stimulated phosphoinositide breakdown in the hypothalamus in a dose-dependent fashion, with SP being more potent than NKA. The NK2-selective antagonist L-659,877, at a dose of 10-6 M, abolished the effect of SP (10-8 M) without affecting basal phosphoinositide breakdown. However, this NK2-selective antagonist did not inhibit the NKA-induced stimulation on phosphoinositide metabolism. The NK-1-selective antagonist L-668,169 stimulated phosphoinositide metabolism at a concentration of 10-6 M, but not at 10-8 M. This NK1-receptor antagonist did not significantly inhibit the effect of SP on phosphoinositide metabolism. Spantide II, another NK1-selective antagonist, also stimulated phosphoinositide metabolism at a dose of 10-6 M. Like L-668,169, spantide II failed to inhibit the SP-induced stimulation of phosphoinositide metabolism, and even potentiated the response to SP. The blockade of the SP-induced phosphoinositide breakdown by the NK2-receptor antagonist (L-659,877), the absence of blockade of the NKA-induced phosphoinositide metabolism by the NK2 receptor antagonist and the absence of inhibition by the NK1 receptor antagonists (L-688,169 and spantide II) suggest that the SP-induced phosphoinositide metabolism in the hypothalamus is mediated by a receptor subclass different from those mediating the peripheral actions of SP.

Original languageEnglish
Pages (from-to)74-79
Number of pages6
JournalBrain research
Volume632
Issue number1-2
DOIs
Publication statusPublished - 1993 Dec 31

Keywords

  • Hypothalamus
  • Neurokinin A
  • Phosphoinositol hydrolysis
  • Senktide
  • Substance P
  • Tachykinin receptor antagonist

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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