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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)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Pharmacy and Pharmacology
volume
48
issue
1
pages
77 - 84
publisher
Pharmaceutical Press
external identifiers
  • pmid:8722501
ISSN
0022-3573
language
English
LU publication?
yes
id
bed7d24b-949e-4a0c-bc2d-3c4e0425c1b9 (old id 1110321)
date added to LUP
2008-07-30 08:49:35
date last changed
2016-04-16 04:56:48
@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    = {Pharmaceutical Press},
  series       = {Journal of Pharmacy and Pharmacology},
  title        = {alpha-Trinositol: a functional (non-receptor) neuropeptide Y antagonist in vasculature},
  volume       = {48},
  year         = {1996},
}