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Studies on the effects of anandamide in rat hepatic artery

Zygmunt, Peter M. LU ; Högestätt, Edward D. LU ; Waldeck, Kristian ; Edwards, Gillian ; Kirkup, Anthony J. and Weston, Arthur H. (1997) In British Journal of Pharmacology 122(8). p.1679-1686
Abstract

1. The effects of anandamide on K+ currents and membrane potential have been examined in freshly-isolated smooth muscle cells from rat hepatic artery and the results compared with the effects of this arachidonic acid derivative on tension and membrane potential changes in segments of whole artery. 2. In the presence of 0.3 mM L-NOARG and 10 μM indomethacin, anandamide (0.1-100 μM) and endothelium-derived hyperpolarizing factor (EDHF; liberated by acetylcholine, 0.01-10 μM) each relaxed endothelium-intact segments of hepatic artery precontracted with phenylephrine. These effects of anandamide, but not those of EDHF, were antagonized by the cannabinoid receptor antagonist, SR141716A (3 μM). 3. The relaxant effects of anandamide... (More)

1. The effects of anandamide on K+ currents and membrane potential have been examined in freshly-isolated smooth muscle cells from rat hepatic artery and the results compared with the effects of this arachidonic acid derivative on tension and membrane potential changes in segments of whole artery. 2. In the presence of 0.3 mM L-NOARG and 10 μM indomethacin, anandamide (0.1-100 μM) and endothelium-derived hyperpolarizing factor (EDHF; liberated by acetylcholine, 0.01-10 μM) each relaxed endothelium-intact segments of hepatic artery precontracted with phenylephrine. These effects of anandamide, but not those of EDHF, were antagonized by the cannabinoid receptor antagonist, SR141716A (3 μM). 3. The relaxant effects of anandamide were unaffected by a toxin combination (apamin plus charybdotoxin, each 0.3 μM) which abolishes EDHF relaxations and were essentially unchanged in endothelium-denuded arteries. The relaxant effects of anandamide in endothelium-intact arteries were significantly reduced in a physiological salt solution containing 30 mM KCl and abolished when the K+ concentration was raised to 60 mM. 4. Anandamide (10 μM), acetylcholine (1 μM, via release of EDHF) and levcromakalim (10 μM) each markedly hyperpolarized the membrane potential of the smooth muscle cells of endothelium-intact arteries. However, when the endothelium was removed, the hyperpolarizing effects of both anandamide (10 μM) and acetylcholine were essentially abolished whereas those of levcromakalim (10 μM) were unaffected. 5. Under voltage-clamp conditions, anandamide (10 μM) abolished spontaneous transient outward currents (STOCs) in freshly-isolated single hepatic artery cells held at 0 mV but had no effect on the holding current at this potential. In current-clamp mode, the spontaneous hyperpolarizing potentials which corresponded to the STOCs were abolished with no significant change in basal membrane potential. 6. Anandamide (10 μM) abolished the iberiotoxin-sensitive K+ current (I(BK(Ca))) produced by caffeine and the corresponding hyperpolarizations generated by this xanthine derivative in current-clamp mode. In contrast, anandamide had no effect on I(BK(Ca)) generated on exposure to NS1619 (30 μM). 7. It was concluded that anandamide is not EDHF in the rat hepatic artery. Anandamide-induced hyperpolarization is exerted indirectly and requires the presence of the endothelium. Anandamide also acts on the smooth muscle cells to inhibit processes which require functional intracellular calcium stores. This direct action seems more important than membrane hyperpolarization in relaxing phenylephrine-contracted vessels.

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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Anandamide, Arteries, hepatic, Endothelium-derived hyperpolarizing factor (EDHF), Intracellular calcium, Potassium currents, Smooth muscle cells, Spontaneous transient outward currents
in
British Journal of Pharmacology
volume
122
issue
8
pages
8 pages
publisher
The British Pharmacological Society
external identifiers
  • scopus:0031463482
  • pmid:9422814
ISSN
0007-1188
DOI
10.1038/sj.bjp.0701601
language
English
LU publication?
no
id
94ecdb5d-6a5c-46cd-bf20-174436da7c40
date added to LUP
2019-05-31 21:38:08
date last changed
2019-12-03 02:12:05
@article{94ecdb5d-6a5c-46cd-bf20-174436da7c40,
  abstract     = {<p>1. The effects of anandamide on K<sup>+</sup> currents and membrane potential have been examined in freshly-isolated smooth muscle cells from rat hepatic artery and the results compared with the effects of this arachidonic acid derivative on tension and membrane potential changes in segments of whole artery. 2. In the presence of 0.3 mM L-NOARG and 10 μM indomethacin, anandamide (0.1-100 μM) and endothelium-derived hyperpolarizing factor (EDHF; liberated by acetylcholine, 0.01-10 μM) each relaxed endothelium-intact segments of hepatic artery precontracted with phenylephrine. These effects of anandamide, but not those of EDHF, were antagonized by the cannabinoid receptor antagonist, SR141716A (3 μM). 3. The relaxant effects of anandamide were unaffected by a toxin combination (apamin plus charybdotoxin, each 0.3 μM) which abolishes EDHF relaxations and were essentially unchanged in endothelium-denuded arteries. The relaxant effects of anandamide in endothelium-intact arteries were significantly reduced in a physiological salt solution containing 30 mM KCl and abolished when the K<sup>+</sup> concentration was raised to 60 mM. 4. Anandamide (10 μM), acetylcholine (1 μM, via release of EDHF) and levcromakalim (10 μM) each markedly hyperpolarized the membrane potential of the smooth muscle cells of endothelium-intact arteries. However, when the endothelium was removed, the hyperpolarizing effects of both anandamide (10 μM) and acetylcholine were essentially abolished whereas those of levcromakalim (10 μM) were unaffected. 5. Under voltage-clamp conditions, anandamide (10 μM) abolished spontaneous transient outward currents (STOCs) in freshly-isolated single hepatic artery cells held at 0 mV but had no effect on the holding current at this potential. In current-clamp mode, the spontaneous hyperpolarizing potentials which corresponded to the STOCs were abolished with no significant change in basal membrane potential. 6. Anandamide (10 μM) abolished the iberiotoxin-sensitive K<sup>+</sup> current (I(BK(Ca))) produced by caffeine and the corresponding hyperpolarizations generated by this xanthine derivative in current-clamp mode. In contrast, anandamide had no effect on I(BK(Ca)) generated on exposure to NS1619 (30 μM). 7. It was concluded that anandamide is not EDHF in the rat hepatic artery. Anandamide-induced hyperpolarization is exerted indirectly and requires the presence of the endothelium. Anandamide also acts on the smooth muscle cells to inhibit processes which require functional intracellular calcium stores. This direct action seems more important than membrane hyperpolarization in relaxing phenylephrine-contracted vessels.</p>},
  author       = {Zygmunt, Peter M. and Högestätt, Edward D. and Waldeck, Kristian and Edwards, Gillian and Kirkup, Anthony J. and Weston, Arthur H.},
  issn         = {0007-1188},
  language     = {eng},
  month        = {12},
  number       = {8},
  pages        = {1679--1686},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Studies on the effects of anandamide in rat hepatic artery},
  url          = {http://dx.doi.org/10.1038/sj.bjp.0701601},
  doi          = {10.1038/sj.bjp.0701601},
  volume       = {122},
  year         = {1997},
}