alpha-Trinositol: a functional (non-receptor) neuropeptide Y antagonist in vasculature

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Neuropeptide Y is a sympathetic co-neurotransmitter released with noradrenaline upon sympathetic nerve stimulation. This study describes the ability of a synthetic inositol phosphate, alpha-trinositol(D-myo-inositol 1,2,6-triphosphate; PP 56) to antagonize vasoconstrictor responses to neuropeptide Y in-vitro as well as in-vivo. In human and guinea-pig isolated arteries alpha-trinositol potently (10 nM to 1 microM extracellular concentration) suppressed the constriction evoked by neuropeptide Y alone, the potentiation by neuropeptide Y of noradrenaline-evoked constriction, and the neuropeptide Y-induced inhibition of relaxation. Moreover, in the pithed (areflexive) rat, a non-adrenergic portion of the pressor response to preganglionic sympathetic nerve stimulation was sensitive to alpha-trinositol. As studied in the recently cloned human (vascular-type) Y1 receptor, the action of alpha-trinositol does not occur through antagonism at the neuropeptide Y recognition site nor does it induce allosteric changes of this receptor. However, we found alpha-trinositol to inhibit the rise in intracellular Ca2+ as well as inositol triphosphate concentrations induced by neuropeptide Y. It is, therefore, proposed that alpha-trinositol represents a non-receptor, but yet selective antagonist of neuropeptide Y in vasculature, opening up the possibility to investigate involvement of neuropeptide Y in sympathetic blood pressure control and in cardiovascular disorders.

Detaljer

Författare
  • X Sun
  • J You
  • T Hedner
  • David Erlinge
  • B Fellström
  • H Yoo
  • C Wahlestedt
  • L Edvinsson
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Kardiologi
Originalspråkengelska
Sidor (från-till)77-84
TidskriftJournal of Pharmacy and Pharmacology
Volym48
Utgåva nummer1
StatusPublished - 1996
PublikationskategoriForskning
Peer review utfördJa