alpha-Trinositol: a functional (non-receptor) neuropeptide Y antagonist in vasculature
Sun, X ; You, J ; Hedner, T ; Erlinge, David LU
; Fellström, B
; Yoo, H
; Wahlestedt, C
and Edvinsson, L
(1996)
In Journal of Pharmacy and Pharmacology
48(1).
p.77-84
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1110321
- author
- Sun, X
; You, J
; Hedner, T
; Erlinge, David
LU
; Fellström, B
; Yoo, H
; Wahlestedt, C
and Edvinsson, L
- organization
- publishing date
- 1996
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Pharmacy and Pharmacology
- volume
- 48
- issue
- 1
- pages
- 77 - 84
- publisher
- Oxford University Press
- external identifiers
-
- pmid:8722501
- scopus:0029923010
- ISSN
- 0022-3573
- language
- English
- LU publication?
- yes
- id
- bed7d24b-949e-4a0c-bc2d-3c4e0425c1b9 (old id 1110321)
- date added to LUP
- 2016-04-01 16:49:50
- date last changed
- 2022-01-28 22:28:34
@article{bed7d24b-949e-4a0c-bc2d-3c4e0425c1b9,
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.}},
author = {{Sun, X and You, J and Hedner, T and Erlinge, David and Fellström, B and Yoo, H and Wahlestedt, C and Edvinsson, L}},
issn = {{0022-3573}},
language = {{eng}},
number = {{1}},
pages = {{77--84}},
publisher = {{Oxford University Press}},
series = {{Journal of Pharmacy and Pharmacology}},
title = {{alpha-Trinositol: a functional (non-receptor) neuropeptide Y antagonist in vasculature}},
volume = {{48}},
year = {{1996}},
}