A novel inositol phosphate selectively inhibits vasoconstriction evoked by the sympathetic co-transmitters neuropeptide Y (NPY) and adenosine triphosphate (ATP)

Claes R Wahlestedt, D. J. Reis, H. Yoo, M. Adamsson, D. Andersson, L. Edvinsson

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Postganglionic sympathetic nerves release norepinephrine (NE) as their primary neurotransmitter at vascular and other targets. However, much evidence supports involvement of additional messengers, co-transmitters, which are co-released with NE upon sympathetic nerve stimulation and thereby contribute to their actions, e.g., vasoconstriction. Two such putative co-transmitters, neuropeptide Y (NPY) and adenosine triphosphate (ATP) have been of particular interest since they fulfill several neurotransmitter criteria. Importantly, hitherto it has been difficult to antagonize vasoconstriction evoked by either NPY or ATP with agents that are devoid of intrinsic activity. The present study describes the ability of a novel inositol phosphate, d-myo-inositol 1,2,6-trisphosphate (Ins[1,2,6]P3; PP-56) to in vitro potently block vasoconstrictor responses elicited by NPY and ATP, but not by NE, as studied in guinea-pig isolated basilar artery. The action of Ins[1,2,6]P3 does not seem to occur through antagonism at NPY-or ATP-receptor recognition sites, labeled by 125I-peptide YY and 35S-γ-ATP, respectively, in membranes of rat cultured vena cava vascular smooth muscle cells. However, it does involve inhibition of the influx of Ca2+ induced by either co-transmitter in these same vena cava cells. It is proposed that Ins[1,2,6]P3 may be a useful functional antagonist of non-adrenergic component(s) of the vasoconstrictor response to sympathetic nerve stimulation.

Original languageEnglish
Pages (from-to)123-126
Number of pages4
JournalNeuroscience Letters
Volume143
Issue number1-2
DOIs
StatePublished - Aug 31 1992
Externally publishedYes

Fingerprint

Inositol Phosphates
Neuropeptide Y
Vasoconstriction
Adenosine Triphosphate
Norepinephrine
Venae Cavae
Vasoconstrictor Agents
Neurotransmitter Agents
Peptide YY
Basilar Artery
Purinergic P1 Receptors
Adrenergic Antagonists
Inositol
Vascular Smooth Muscle
Smooth Muscle Myocytes
Blood Vessels
Guinea Pigs
Membranes

Keywords

  • ATP
  • Co-transmitter
  • Inositol phosphate
  • Neuropeptide Y
  • Norepinephrine
  • Sympathetic nerve
  • Vasoconstriction

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A novel inositol phosphate selectively inhibits vasoconstriction evoked by the sympathetic co-transmitters neuropeptide Y (NPY) and adenosine triphosphate (ATP). / Wahlestedt, Claes R; Reis, D. J.; Yoo, H.; Adamsson, M.; Andersson, D.; Edvinsson, L.

In: Neuroscience Letters, Vol. 143, No. 1-2, 31.08.1992, p. 123-126.

Research output: Contribution to journalArticle

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abstract = "Postganglionic sympathetic nerves release norepinephrine (NE) as their primary neurotransmitter at vascular and other targets. However, much evidence supports involvement of additional messengers, co-transmitters, which are co-released with NE upon sympathetic nerve stimulation and thereby contribute to their actions, e.g., vasoconstriction. Two such putative co-transmitters, neuropeptide Y (NPY) and adenosine triphosphate (ATP) have been of particular interest since they fulfill several neurotransmitter criteria. Importantly, hitherto it has been difficult to antagonize vasoconstriction evoked by either NPY or ATP with agents that are devoid of intrinsic activity. The present study describes the ability of a novel inositol phosphate, d-myo-inositol 1,2,6-trisphosphate (Ins[1,2,6]P3; PP-56) to in vitro potently block vasoconstrictor responses elicited by NPY and ATP, but not by NE, as studied in guinea-pig isolated basilar artery. The action of Ins[1,2,6]P3 does not seem to occur through antagonism at NPY-or ATP-receptor recognition sites, labeled by 125I-peptide YY and 35S-γ-ATP, respectively, in membranes of rat cultured vena cava vascular smooth muscle cells. However, it does involve inhibition of the influx of Ca2+ induced by either co-transmitter in these same vena cava cells. It is proposed that Ins[1,2,6]P3 may be a useful functional antagonist of non-adrenergic component(s) of the vasoconstrictor response to sympathetic nerve stimulation.",
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