Perivascular expression and potent vasoconstrictor effect of dynorphin A in cerebral arteries.

<h4>Background</h4>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 th...

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Autores principales: Éva Ruisanchez, Attila Cselenyák, Rege Sugárka Papp, Tamás Németh, Krisztina Káldi, Péter Sándor, Zoltán Benyó
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spelling oai:doaj.org-article:12139814be754ad2833db34fa432b30f2021-11-18T07:17:16ZPerivascular expression and potent vasoconstrictor effect of dynorphin A in cerebral arteries.1932-620310.1371/journal.pone.0037798https://doaj.org/article/12139814be754ad2833db34fa432b30f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22662226/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 G(i/o)-protein mediated signaling by pertussis toxin. Finally, des-Tyr(1) 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.<h4>Conclusion/significance</h4>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 G(i/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.Éva RuisanchezAttila CselenyákRege Sugárka PappTamás NémethKrisztina KáldiPéter SándorZoltán BenyóPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37798 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Éva Ruisanchez
Attila Cselenyák
Rege Sugárka Papp
Tamás Németh
Krisztina Káldi
Péter Sándor
Zoltán Benyó
Perivascular expression and potent vasoconstrictor effect of dynorphin A in cerebral arteries.
description <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 G(i/o)-protein mediated signaling by pertussis toxin. Finally, des-Tyr(1) 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.<h4>Conclusion/significance</h4>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 G(i/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.
format article
author Éva Ruisanchez
Attila Cselenyák
Rege Sugárka Papp
Tamás Németh
Krisztina Káldi
Péter Sándor
Zoltán Benyó
author_facet Éva Ruisanchez
Attila Cselenyák
Rege Sugárka Papp
Tamás Németh
Krisztina Káldi
Péter Sándor
Zoltán Benyó
author_sort Éva Ruisanchez
title Perivascular expression and potent vasoconstrictor effect of dynorphin A in cerebral arteries.
title_short Perivascular expression and potent vasoconstrictor effect of dynorphin A in cerebral arteries.
title_full Perivascular expression and potent vasoconstrictor effect of dynorphin A in cerebral arteries.
title_fullStr Perivascular expression and potent vasoconstrictor effect of dynorphin A in cerebral arteries.
title_full_unstemmed Perivascular expression and potent vasoconstrictor effect of dynorphin A in cerebral arteries.
title_sort perivascular expression and potent vasoconstrictor effect of dynorphin a in cerebral arteries.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/12139814be754ad2833db34fa432b30f
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