Perivascular expression and potent vasoconstrictor effect of dynorphin a in cerebral arteries

Éva Ruisanchez, Attila Cselenyák, Rege Sugárka Papp, Tamás Németh, K. Káldi, Péter Sándor, Zoltán Benyó

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Numerous literary data indicate that dynorphin A (DYN-A) has a significant impact on cerebral circulation, especially under pathophysiological conditions, but its potential direct influence on the tone of cerebral vessels is obscure. The aim of the present study was threefold: 1) to clarify if DYN-A is present in cerebral vessels, 2) to determine if it exerts any direct effect on cerebrovascular tone, and if so, 3) to analyze the role of κ-opiate receptors in mediating the effect. Methodology/Principal Findings: Immunohistochemical analysis revealed the expression of DYN-A in perivascular nerves of rat pial arteries as well as in both rat and human intraparenchymal vessels of the cerebral cortex. In isolated rat basilar and middle cerebral arteries (BAs and MCAs) DYN-A (1-13) and DYN-A (1-17) but not DYN-A (1-8) or dynorphin B (DYN-B) induced strong vasoconstriction in micromolar concentrations. The maximal effects, compared to a reference contraction induced by 124 mM K+, were 115±6% and 104±10% in BAs and 113±3% and 125±9% in MCAs for 10 μM of DYN-A (1-13) and DYN-A (1-17), respectively. The vasoconstrictor effects of DYN-A (1-13) could be inhibited but not abolished by both the κ-opiate receptor antagonist nor-Binaltorphimine dihydrochloride (NORBI) and blockade of Gi/o-protein mediated signaling by pertussis toxin. Finally, des-Tyr1 DYN-A (2-13), which reportedly fails to activate κ-opiate receptors, induced vasoconstriction of 45±11% in BAs and 50±5% in MCAs at 10 μM, which effects were resistant to NORBI. Conclusion/Significance: DYN-A is present in rat and human cerebral perivascular nerves and induces sustained contraction of rat cerebral arteries. This vasoconstrictor effect is only partly mediated by κ-opiate receptors and heterotrimeric Gi/o-proteins. To our knowledge our present findings are the first to indicate that DYN-A has a direct cerebral vasoconstrictor effect and that a dynorphin-induced vascular action may be, at least in part, independent of κ-opiate receptors.

Original languageEnglish
Article numbere37798
JournalPLoS One
Volume7
Issue number5
DOIs
Publication statusPublished - May 25 2012

Fingerprint

vasoconstrictor agents
Dynorphins
Cerebral Arteries
Vasoconstrictor Agents
arteries
Opioid Receptors
receptors
rats
Rats
vasoconstriction
nerve tissue
dynorphin (1-8)
pertussis toxin
Vasoconstriction
cerebral cortex
Cerebrovascular Circulation
blood vessels
antagonists
proteins
Pertussis Toxin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ruisanchez, É., Cselenyák, A., Papp, R. S., Németh, T., Káldi, K., Sándor, P., & Benyó, Z. (2012). Perivascular expression and potent vasoconstrictor effect of dynorphin a in cerebral arteries. PLoS One, 7(5), [e37798]. https://doi.org/10.1371/journal.pone.0037798

Perivascular expression and potent vasoconstrictor effect of dynorphin a in cerebral arteries. / Ruisanchez, Éva; Cselenyák, Attila; Papp, Rege Sugárka; Németh, Tamás; Káldi, K.; Sándor, Péter; Benyó, Zoltán.

In: PLoS One, Vol. 7, No. 5, e37798, 25.05.2012.

Research output: Contribution to journalArticle

Ruisanchez, É, Cselenyák, A, Papp, RS, Németh, T, Káldi, K, Sándor, P & Benyó, Z 2012, 'Perivascular expression and potent vasoconstrictor effect of dynorphin a in cerebral arteries', PLoS One, vol. 7, no. 5, e37798. https://doi.org/10.1371/journal.pone.0037798
Ruisanchez, Éva ; Cselenyák, Attila ; Papp, Rege Sugárka ; Németh, Tamás ; Káldi, K. ; Sándor, Péter ; Benyó, Zoltán. / Perivascular expression and potent vasoconstrictor effect of dynorphin a in cerebral arteries. In: PLoS One. 2012 ; Vol. 7, No. 5.
@article{f8430b96e1d147a98f2cedd99af48229,
title = "Perivascular expression and potent vasoconstrictor effect of dynorphin a in cerebral arteries",
abstract = "Background: Numerous literary data indicate that dynorphin A (DYN-A) has a significant impact on cerebral circulation, especially under pathophysiological conditions, but its potential direct influence on the tone of cerebral vessels is obscure. The aim of the present study was threefold: 1) to clarify if DYN-A is present in cerebral vessels, 2) to determine if it exerts any direct effect on cerebrovascular tone, and if so, 3) to analyze the role of κ-opiate receptors in mediating the effect. Methodology/Principal Findings: Immunohistochemical analysis revealed the expression of DYN-A in perivascular nerves of rat pial arteries as well as in both rat and human intraparenchymal vessels of the cerebral cortex. In isolated rat basilar and middle cerebral arteries (BAs and MCAs) DYN-A (1-13) and DYN-A (1-17) but not DYN-A (1-8) or dynorphin B (DYN-B) induced strong vasoconstriction in micromolar concentrations. The maximal effects, compared to a reference contraction induced by 124 mM K+, were 115±6{\%} and 104±10{\%} in BAs and 113±3{\%} and 125±9{\%} in MCAs for 10 μM of DYN-A (1-13) and DYN-A (1-17), respectively. The vasoconstrictor effects of DYN-A (1-13) could be inhibited but not abolished by both the κ-opiate receptor antagonist nor-Binaltorphimine dihydrochloride (NORBI) and blockade of Gi/o-protein mediated signaling by pertussis toxin. Finally, des-Tyr1 DYN-A (2-13), which reportedly fails to activate κ-opiate receptors, induced vasoconstriction of 45±11{\%} in BAs and 50±5{\%} in MCAs at 10 μM, which effects were resistant to NORBI. Conclusion/Significance: DYN-A is present in rat and human cerebral perivascular nerves and induces sustained contraction of rat cerebral arteries. This vasoconstrictor effect is only partly mediated by κ-opiate receptors and heterotrimeric Gi/o-proteins. To our knowledge our present findings are the first to indicate that DYN-A has a direct cerebral vasoconstrictor effect and that a dynorphin-induced vascular action may be, at least in part, independent of κ-opiate receptors.",
author = "{\'E}va Ruisanchez and Attila Cseleny{\'a}k and Papp, {Rege Sug{\'a}rka} and Tam{\'a}s N{\'e}meth and K. K{\'a}ldi and P{\'e}ter S{\'a}ndor and Zolt{\'a}n Beny{\'o}",
year = "2012",
month = "5",
day = "25",
doi = "10.1371/journal.pone.0037798",
language = "English",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

TY - JOUR

T1 - Perivascular expression and potent vasoconstrictor effect of dynorphin a in cerebral arteries

AU - Ruisanchez, Éva

AU - Cselenyák, Attila

AU - Papp, Rege Sugárka

AU - Németh, Tamás

AU - Káldi, K.

AU - Sándor, Péter

AU - Benyó, Zoltán

PY - 2012/5/25

Y1 - 2012/5/25

N2 - Background: Numerous literary data indicate that dynorphin A (DYN-A) has a significant impact on cerebral circulation, especially under pathophysiological conditions, but its potential direct influence on the tone of cerebral vessels is obscure. The aim of the present study was threefold: 1) to clarify if DYN-A is present in cerebral vessels, 2) to determine if it exerts any direct effect on cerebrovascular tone, and if so, 3) to analyze the role of κ-opiate receptors in mediating the effect. Methodology/Principal Findings: Immunohistochemical analysis revealed the expression of DYN-A in perivascular nerves of rat pial arteries as well as in both rat and human intraparenchymal vessels of the cerebral cortex. In isolated rat basilar and middle cerebral arteries (BAs and MCAs) DYN-A (1-13) and DYN-A (1-17) but not DYN-A (1-8) or dynorphin B (DYN-B) induced strong vasoconstriction in micromolar concentrations. The maximal effects, compared to a reference contraction induced by 124 mM K+, were 115±6% and 104±10% in BAs and 113±3% and 125±9% in MCAs for 10 μM of DYN-A (1-13) and DYN-A (1-17), respectively. The vasoconstrictor effects of DYN-A (1-13) could be inhibited but not abolished by both the κ-opiate receptor antagonist nor-Binaltorphimine dihydrochloride (NORBI) and blockade of Gi/o-protein mediated signaling by pertussis toxin. Finally, des-Tyr1 DYN-A (2-13), which reportedly fails to activate κ-opiate receptors, induced vasoconstriction of 45±11% in BAs and 50±5% in MCAs at 10 μM, which effects were resistant to NORBI. Conclusion/Significance: DYN-A is present in rat and human cerebral perivascular nerves and induces sustained contraction of rat cerebral arteries. This vasoconstrictor effect is only partly mediated by κ-opiate receptors and heterotrimeric Gi/o-proteins. To our knowledge our present findings are the first to indicate that DYN-A has a direct cerebral vasoconstrictor effect and that a dynorphin-induced vascular action may be, at least in part, independent of κ-opiate receptors.

AB - Background: Numerous literary data indicate that dynorphin A (DYN-A) has a significant impact on cerebral circulation, especially under pathophysiological conditions, but its potential direct influence on the tone of cerebral vessels is obscure. The aim of the present study was threefold: 1) to clarify if DYN-A is present in cerebral vessels, 2) to determine if it exerts any direct effect on cerebrovascular tone, and if so, 3) to analyze the role of κ-opiate receptors in mediating the effect. Methodology/Principal Findings: Immunohistochemical analysis revealed the expression of DYN-A in perivascular nerves of rat pial arteries as well as in both rat and human intraparenchymal vessels of the cerebral cortex. In isolated rat basilar and middle cerebral arteries (BAs and MCAs) DYN-A (1-13) and DYN-A (1-17) but not DYN-A (1-8) or dynorphin B (DYN-B) induced strong vasoconstriction in micromolar concentrations. The maximal effects, compared to a reference contraction induced by 124 mM K+, were 115±6% and 104±10% in BAs and 113±3% and 125±9% in MCAs for 10 μM of DYN-A (1-13) and DYN-A (1-17), respectively. The vasoconstrictor effects of DYN-A (1-13) could be inhibited but not abolished by both the κ-opiate receptor antagonist nor-Binaltorphimine dihydrochloride (NORBI) and blockade of Gi/o-protein mediated signaling by pertussis toxin. Finally, des-Tyr1 DYN-A (2-13), which reportedly fails to activate κ-opiate receptors, induced vasoconstriction of 45±11% in BAs and 50±5% in MCAs at 10 μM, which effects were resistant to NORBI. Conclusion/Significance: DYN-A is present in rat and human cerebral perivascular nerves and induces sustained contraction of rat cerebral arteries. This vasoconstrictor effect is only partly mediated by κ-opiate receptors and heterotrimeric Gi/o-proteins. To our knowledge our present findings are the first to indicate that DYN-A has a direct cerebral vasoconstrictor effect and that a dynorphin-induced vascular action may be, at least in part, independent of κ-opiate receptors.

UR - http://www.scopus.com/inward/record.url?scp=84861476277&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861476277&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0037798

DO - 10.1371/journal.pone.0037798

M3 - Article

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 5

M1 - e37798

ER -