α-trinositol: A functional (non-receptor) neuropeptide Y antagonist in vasculature

Xiangying Sun, Junping You, Thomas Hedner, David Erlinge, Bengt Fellström, Heahyun Yoo, Claes R Wahlestedt, Lars Edvinsson

Research output: Contribution to journalArticle

6 Citations (Scopus)

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, α-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 α-trinositol potently (10 nM to 1 μM 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 presser response to preganglionic sympathetic nerve stimulation was sensitive to α-trinositol. As studied in the recently cloned human (vascular-type) Y1 receptor, the action of α-trinositol does not occur through antagonism at the neuropeptide Y recognition site nor does it induce allosteric changes of this receptor. However, we found α-trinositol to inhibit the rise in intracellular Ca2+ as well as inositol triphosphate concentrations induced by neuropeptide Y. It is, therefore, proposed that α-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.

Original languageEnglish
Pages (from-to)77-84
Number of pages8
JournalJournal of Pharmacy and Pharmacology
Volume48
Issue number1
StatePublished - May 9 1996
Externally publishedYes

Fingerprint

Neuropeptide Y
Constriction
Norepinephrine
Inositol Phosphates
Vasoconstrictor Agents
Inositol
Neurotransmitter Agents
Blood Vessels
Guinea Pigs
Arteries
Blood Pressure

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Sun, X., You, J., Hedner, T., Erlinge, D., Fellström, B., Yoo, H., ... Edvinsson, L. (1996). α-trinositol: A functional (non-receptor) neuropeptide Y antagonist in vasculature. Journal of Pharmacy and Pharmacology, 48(1), 77-84.

α-trinositol : A functional (non-receptor) neuropeptide Y antagonist in vasculature. / Sun, Xiangying; You, Junping; Hedner, Thomas; Erlinge, David; Fellström, Bengt; Yoo, Heahyun; Wahlestedt, Claes R; Edvinsson, Lars.

In: Journal of Pharmacy and Pharmacology, Vol. 48, No. 1, 09.05.1996, p. 77-84.

Research output: Contribution to journalArticle

Sun, X, You, J, Hedner, T, Erlinge, D, Fellström, B, Yoo, H, Wahlestedt, CR & Edvinsson, L 1996, 'α-trinositol: A functional (non-receptor) neuropeptide Y antagonist in vasculature', Journal of Pharmacy and Pharmacology, vol. 48, no. 1, pp. 77-84.
Sun X, You J, Hedner T, Erlinge D, Fellström B, Yoo H et al. α-trinositol: A functional (non-receptor) neuropeptide Y antagonist in vasculature. Journal of Pharmacy and Pharmacology. 1996 May 9;48(1):77-84.
Sun, Xiangying ; You, Junping ; Hedner, Thomas ; Erlinge, David ; Fellström, Bengt ; Yoo, Heahyun ; Wahlestedt, Claes R ; Edvinsson, Lars. / α-trinositol : A functional (non-receptor) neuropeptide Y antagonist in vasculature. In: Journal of Pharmacy and Pharmacology. 1996 ; Vol. 48, No. 1. pp. 77-84.
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