Presence of Contractile Endothelin-A and Dilatory Endothelin-B Receptors in Human Cerebral Arteries

Nilsson, T.; Cantera, Leonor; Adner, Mikael; Edvinsson, Lars

doi:10.1097/00006123-199702000-00023

Cited by 76 publications

(51 citation statements)

References 31 publications

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“…RT-PCR experiments indicated the presence of mRNAs for both endothelin receptor subtypes ETA and ETB in the fibers. These observations were consistent with these earlier studies by functional analysis and RT-PCR (20,21).…”

Section: Discussionsupporting

confidence: 94%

Contractile Responses and Myosin Phosphorylation in Reconstituted Fibers of Smooth Muscle Cells From the Rat Cerebral Artery

Oishi

Takatoh

Bao

et al. 2002

Japanese Journal of Pharmacology

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ABSTRACT-String-shaped reconstituted smooth muscle fibers were prepared in rectangular wells by thermal gelation of a mixed solution of collagen and cultured smooth muscle cells derived from the rat cerebral artery. The fibers contracted in response to KCl, 5-hydroxytryptamine (5-HT), noradrenaline, endothelin-1, endothelin-2, angiotensin II, prostaglandin F 2= and prostaglandin E 2 . 5-HT-induced contraction was partially inhibited by the L-type voltage-dependent Ca 2+ channel inhibitor nifedipine, putative non-selective cationic channel inhibitor SKF96365 and intracellular Ca 2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM), and completely abolished by the myosin light chain kinase inhibitor ML-9. The fibers pre-contracted by 5-HT were completely relaxed by the Rho kinase inhibitor Y-27632, serine /threonine kinase inhibitor staurosporine, 8-bromo cyclic GMP and papaverine, and partially relaxed by dibutyryl cyclic AMP. Moreover, 5-HT as well as endothelin-1 and KCl enhanced 20-kDa myosin light chain phosphorylation in the fibers. These results suggested that the characteristics of contraction of the fibers reflect typical contractilities of vascular smooth muscle tissues. This technique will allow us to directly address questions relating to heterogeneity of receptor mechanisms and intracellular pathways of vascular smooth muscle contraction as a function of vessel type.

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Section: Discussionsupporting

confidence: 94%

Contractile Responses and Myosin Phosphorylation in Reconstituted Fibers of Smooth Muscle Cells From the Rat Cerebral Artery

Oishi

Takatoh

Bao

et al. 2002

Japanese Journal of Pharmacology

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“…This treatment caused a leftwards shift of the dose-response curves for ET-1 (indicating increased sensitivity to ET-1) and the appearance of a strong ET B -specific contractile response to S6c (Hansen-Schwartz et al, 2002a;Nilsson et al, 1997). The time course of endothelin receptor changes in cultured MCAs is relatively fast, with a small contractile response to S6c after just 6 hours of organ culture (Henriksson et al, 2003;Kristiansen et al, 2011).…”

Section: Organ Culture As a Methods To Investigate Cerebrovascular Recmentioning

confidence: 99%

“…To address the first part of this question, small samples of cortex arterioles were obtained in conjunction with neurosurgical tumor resections or operations to remove epileptic seizure areas. These vessels indeed express ET A and ET B receptors (Nilsson et al, 1997), AT 1 (Ahnstedt et al, 2011; Ansar et al, 2009), 5-HT 1B (Nilsson et al, 1999), and thromboxane A2 (Uski et al, 1983) receptors. Moreover, freshly obtained human cerebral arteries exhibit ET-1-induced responses that were found to be similar to the responses observed in fresh rat cerebral arteries; ET-1 elicited an ET A receptor-mediated contraction with E max 112% and pEC 50 9.2, whereas S6c elicited an ET B receptor-mediated dilatation on precontraction (Nilsson et al, 1997).…”

Section: Cerebrovascular Receptor Changes In Human Arteriesmentioning

confidence: 99%

Vascular plasticity in cerebrovascular disorders

Edvinsson

Povlsen

2011

J Cereb Blood Flow Metab

115

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Cerebral ischemia remains a major cause of morbidity and mortality with little advancement in subacute treatment options. This review aims to cover and discuss novel insight obtained during the last decade into plastic changes in the vasoconstrictor receptor profiles of cerebral arteries and microvessels that takes place after different types of stroke. Receptors like the endothelin type B, angiotensin type 1, and 5-hydroxytryptamine type 1B/1D receptors are upregulated in the smooth muscle layer of cerebral arteries after different types of ischemic stroke as well as after subarachnoid hemorrhage, yielding rather dramatic changes in the contractility of the vessels. Some of the signal transduction processes mediating this receptor upregulation have been elucidated. In particular the extracellular regulated kinase 1/2 pathway, which is activated early in the process, has proven to be a promising therapeutic target for prevention of vasoconstrictor receptor upregulation after stroke. Together, those findings provide new perspectives on the pathophysiology of ischemic stroke and point toward a novel way of reducing vasoconstriction, neuronal cell death, and thus neurologic deficits after stroke.

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“…Both are G-protein coupled receptors of which the ET A receptor is localized on smooth muscle cells in the cerebrovascular wall and stimulates proliferation and vasoconstriction, while the ET B receptors are mainly situated on endothelial cells, mediating vasodilatation (Nilsson et al 1997;Szok et al 2001). The endothelin system has been shown to be involved in several pathophysiological conditions, such as atherosclerosis (Iwasa et al 1999), heart failure (Miyauchi and Goto 1999) and ischaemic stroke (Ziv et al 1992;Barone et al 1994;Lampl et al 1997).…”

Section: Introductionmentioning

confidence: 99%

MEK1/2 inhibition attenuates vascular ETA and ETB receptor alterations after cerebral ischaemia

et al. 2006

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Presence of Contractile Endothelin-A and Dilatory Endothelin-B Receptors in Human Cerebral Arteries

Abstract: The ET-1-induced vasoconstriction of human cerebral arteries is primarily mediated by the ETA receptor, whereas the sarafotoxin 6c-induced vasodilatation seems to be mediated via the ETB receptor.

Cited by 76 publications

References 31 publications

Contractile Responses and Myosin Phosphorylation in Reconstituted Fibers of Smooth Muscle Cells From the Rat Cerebral Artery

Contractile Responses and Myosin Phosphorylation in Reconstituted Fibers of Smooth Muscle Cells From the Rat Cerebral Artery

Vascular plasticity in cerebrovascular disorders

MEK1/2 inhibition attenuates vascular ETA and ETB receptor alterations after cerebral ischaemia

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