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 language | English |
|---|---|
| Pages (from-to) | 77-84 |
| Number of pages | 8 |
| Journal | Journal of Pharmacy and Pharmacology |
| Volume | 48 |
| Issue number | 1 |
| State | Published - May 9 1996 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science
Cite this
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 journal › Article
}
TY - JOUR
T1 - α-trinositol
T2 - A functional (non-receptor) neuropeptide Y antagonist in vasculature
AU - Sun, Xiangying
AU - You, Junping
AU - Hedner, Thomas
AU - Erlinge, David
AU - Fellström, Bengt
AU - Yoo, Heahyun
AU - Wahlestedt, Claes R
AU - Edvinsson, Lars
PY - 1996/5/9
Y1 - 1996/5/9
N2 - 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.
AB - 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.
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M3 - Article
C2 - 8722501
AN - SCOPUS:0029923010
VL - 48
SP - 77
EP - 84
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
SN - 0022-3573
IS - 1
ER -