Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You and Your Team.

Learn More →

U-46619 but not serotonin increases endocannabinoid content in middle cerebral artery: evidence for functional relevance

U-46619 but not serotonin increases endocannabinoid content in middle cerebral artery: evidence... Cerebral vascular smooth muscle cells express the CB 1 cannabinoid receptor, and CB 1 receptor agonists produce vasodilation of cerebral arteries. The purpose of this study was to determine whether vasoconstriction of rat middle cerebral artery (MCA) results in the local formation of endocannabinoids (eCBs), which, via activation of CB 1 receptors, oppose the vasoconstriction in a feedback manner. The thromboxane A 2 (TXA 2 ) mimetic U-46619 significantly increased N -arachidonylethanolamine (AEA) and 2-arachidonylglycerol (2-AG) content of isolated MCA, whereas 5-hydroxytrypamine (5-HT) decreased AEA and 2-AG content. If eCBs play a feedback role in the regulation of MCA tone, then CB 1 receptor antagonists should enhance the constriction of MCA produced by U-46619 but not 5-HT. U-46619 caused concentration-dependent constrictions of endothelium-denuded MCA. Two CB 1 receptor antagonists SR-141716 and AM-251 decreased the EC 50 value for U-46619 to constrict endothelium-denuded MCA without affecting the maximal effect. A low concentration of CB 1 receptor agonist Win-55212-2 (30 nM) produced vasodilation of MCAs constricted with low but not saturating concentrations of U-46619. SR-141716 had no effect on the 5-HT concentration-contraction relationship. These data suggest that TXA 2 receptor activation increases MCA eCB content, which, via activation of CB 1 receptors, reduces the constriction produced by moderate concentrations of the TXA 2 agonist. Although 5-HT-induced vasoconstriction is reduced by exogenous CB 1 receptor agonist, activation of 5-HT receptors does not increase eCB content. These results suggest that MCA production of eCBs is not regulated by constriction per se but likely via a signaling pathway that is specific for TXA 2 receptors and not 5-HT receptors. CB 1 receptor; cannabinoids; SR-141716; AM-251; N -arachidonylethanolamine; 2-arachidonylglycerol; mass spectrometry Address for reprint requests and other correspondence: Cecilia J. Hillard, Medical College of Wisconsin, Dept. of Pharmacology and Toxicology, 8701 Watertown Plank Rd., Milwaukee, WI 53226-0509 (E-mail: chillard@mcw.edu ) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Heart and Circulatory Physiology The American Physiological Society

U-46619 but not serotonin increases endocannabinoid content in middle cerebral artery: evidence for functional relevance

Loading next page...
 
/lp/the-american-physiological-society/u-46619-but-not-serotonin-increases-endocannabinoid-content-in-middle-CvCWJMS8GU
Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6135
eISSN
1522-1539
DOI
10.1152/ajpheart.00978.2004
pmid
15695564
Publisher site
See Article on Publisher Site

Abstract

Cerebral vascular smooth muscle cells express the CB 1 cannabinoid receptor, and CB 1 receptor agonists produce vasodilation of cerebral arteries. The purpose of this study was to determine whether vasoconstriction of rat middle cerebral artery (MCA) results in the local formation of endocannabinoids (eCBs), which, via activation of CB 1 receptors, oppose the vasoconstriction in a feedback manner. The thromboxane A 2 (TXA 2 ) mimetic U-46619 significantly increased N -arachidonylethanolamine (AEA) and 2-arachidonylglycerol (2-AG) content of isolated MCA, whereas 5-hydroxytrypamine (5-HT) decreased AEA and 2-AG content. If eCBs play a feedback role in the regulation of MCA tone, then CB 1 receptor antagonists should enhance the constriction of MCA produced by U-46619 but not 5-HT. U-46619 caused concentration-dependent constrictions of endothelium-denuded MCA. Two CB 1 receptor antagonists SR-141716 and AM-251 decreased the EC 50 value for U-46619 to constrict endothelium-denuded MCA without affecting the maximal effect. A low concentration of CB 1 receptor agonist Win-55212-2 (30 nM) produced vasodilation of MCAs constricted with low but not saturating concentrations of U-46619. SR-141716 had no effect on the 5-HT concentration-contraction relationship. These data suggest that TXA 2 receptor activation increases MCA eCB content, which, via activation of CB 1 receptors, reduces the constriction produced by moderate concentrations of the TXA 2 agonist. Although 5-HT-induced vasoconstriction is reduced by exogenous CB 1 receptor agonist, activation of 5-HT receptors does not increase eCB content. These results suggest that MCA production of eCBs is not regulated by constriction per se but likely via a signaling pathway that is specific for TXA 2 receptors and not 5-HT receptors. CB 1 receptor; cannabinoids; SR-141716; AM-251; N -arachidonylethanolamine; 2-arachidonylglycerol; mass spectrometry Address for reprint requests and other correspondence: Cecilia J. Hillard, Medical College of Wisconsin, Dept. of Pharmacology and Toxicology, 8701 Watertown Plank Rd., Milwaukee, WI 53226-0509 (E-mail: chillard@mcw.edu )

Journal

AJP - Heart and Circulatory PhysiologyThe American Physiological Society

Published: Jun 1, 2005

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$499/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month