Cat cerebral arterial smooth muscle cells express cytochrome P450 4A2 enzyme and produce the vasoconstrictor 20-HETE which enhances L-type Ca2+ current
Cerebral arteries express cytochrome P450 4A enzymes (P450 4A) and produce 20- hydroxyeicosatetraenoic acid (20-HETE), a potent constrictor of pial arterioles. It is not known which cell type in the vessel wall is responsible for the formation of 20-HETE. We examined whether freshly isolated cerebra...
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| Veröffentlicht in: | The Journal of physiology 1998-03, Vol.507 (3), p.771-781 |
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| creator | Gebremedhin, Debebe Lange, Andrew R. Narayanan, Jayashree Aebly, Mikael R. Jacobs, Elizabeth R. Harder, David R. |
| description | Cerebral arteries express cytochrome P450 4A enzymes (P450 4A) and produce 20- hydroxyeicosatetraenoic acid (20-HETE), a potent
constrictor of pial arterioles. It is not known which cell type in the vessel wall is responsible for the formation of 20-HETE.
We examined whether freshly isolated cerebral arterial muscle cells (VSMCs) express P450 4A and produce 20-HETE. We also studied
the effect of 20-HETE on pressurized cerebral arteries and on whole-cell L-type Ca 2+ current ( I Ca ) recorded in cat cerebral VSMCs.
Cat cerebral VSMCs incubated with [ 14 C]arachidonic acid ([ 14 C]AA) produced 20-HETE (3.9 ± 1.1 pmol min â1 (mg protein) â1 ).
Reverse transcription-polymerase chain reaction studies revealed that cat cerebral VSMCs express mRNA for P450 4A which metabolizes
AA to 20-HETE. Cloning and sequencing of the cDNA amplified from mRNA isolated from VSMCs showed > 96% amino acid homology
to the rat and human P450 4A2 and 4A3.
20-HETE (1â300 n m ) induced a concentration-dependent constriction of cat cerebral arteries, which was inhibited by nifedipine.
Addition of 10 and 100 n m 20-HETE to the bath increased peak I Ca by 50 ± 3 and 100 ± 10%, respectively. This effect was not influenced by altering the frequency of depolarization. 20-HETE
(100 n m ) failed to increase I Ca in the presence of nifedipine.
These results demonstrate that cat cerebral VSMCs express P450 4A enzyme, and produce 20-HETE which activates L-type Ca 2+ channel current to promote cerebral vasoconstriction. |
| doi_str_mv | 10.1111/j.1469-7793.1998.771bs.x |
| format | Article |
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constrictor of pial arterioles. It is not known which cell type in the vessel wall is responsible for the formation of 20-HETE.
We examined whether freshly isolated cerebral arterial muscle cells (VSMCs) express P450 4A and produce 20-HETE. We also studied
the effect of 20-HETE on pressurized cerebral arteries and on whole-cell L-type Ca 2+ current ( I Ca ) recorded in cat cerebral VSMCs.
Cat cerebral VSMCs incubated with [ 14 C]arachidonic acid ([ 14 C]AA) produced 20-HETE (3.9 ± 1.1 pmol min â1 (mg protein) â1 ).
Reverse transcription-polymerase chain reaction studies revealed that cat cerebral VSMCs express mRNA for P450 4A which metabolizes
AA to 20-HETE. Cloning and sequencing of the cDNA amplified from mRNA isolated from VSMCs showed > 96% amino acid homology
to the rat and human P450 4A2 and 4A3.
20-HETE (1â300 n m ) induced a concentration-dependent constriction of cat cerebral arteries, which was inhibited by nifedipine.
Addition of 10 and 100 n m 20-HETE to the bath increased peak I Ca by 50 ± 3 and 100 ± 10%, respectively. This effect was not influenced by altering the frequency of depolarization. 20-HETE
(100 n m ) failed to increase I Ca in the presence of nifedipine.
These results demonstrate that cat cerebral VSMCs express P450 4A enzyme, and produce 20-HETE which activates L-type Ca 2+ channel current to promote cerebral vasoconstriction.</description><identifier>ISSN: 0022-3751</identifier><identifier>EISSN: 1469-7793</identifier><identifier>DOI: 10.1111/j.1469-7793.1998.771bs.x</identifier><identifier>PMID: 9508838</identifier><language>eng</language><publisher>Oxford, UK: The Physiological Society</publisher><subject>Amino Acid Sequence ; Animals ; Arachidonic Acid - metabolism ; Cats ; Cerebral Arteries - metabolism ; Cerebral Arteries - physiology ; Cloning, Molecular ; Cytochrome P-450 CYP4A ; Cytochrome P-450 Enzyme System - biosynthesis ; Cytochrome P-450 Enzyme System - chemistry ; DNA Primers ; Humans ; Hydroxyeicosatetraenoic Acids - metabolism ; Hydroxyeicosatetraenoic Acids - pharmacology ; In Vitro Techniques ; Membrane Potentials - drug effects ; Membrane Potentials - physiology ; Mixed Function Oxygenases - biosynthesis ; Mixed Function Oxygenases - chemistry ; Molecular Sequence Data ; Muscle, Smooth, Vascular - metabolism ; Muscle, Smooth, Vascular - physiology ; Nifedipine - pharmacology ; Original ; Polymerase Chain Reaction ; Rats ; RNA, Messenger - biosynthesis ; Sequence Alignment ; Sequence Homology, Amino Acid ; Transcription, Genetic ; Vasoconstriction - drug effects ; Vasoconstriction - physiology ; Vasoconstrictor Agents - pharmacology</subject><ispartof>The Journal of physiology, 1998-03, Vol.507 (3), p.771-781</ispartof><rights>1998 The Journal of Physiology © 1998 The Physiological Society</rights><rights>The Physiological Society 1998 1998</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2230829/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2230829/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9508838$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gebremedhin, Debebe</creatorcontrib><creatorcontrib>Lange, Andrew R.</creatorcontrib><creatorcontrib>Narayanan, Jayashree</creatorcontrib><creatorcontrib>Aebly, Mikael R.</creatorcontrib><creatorcontrib>Jacobs, Elizabeth R.</creatorcontrib><creatorcontrib>Harder, David R.</creatorcontrib><title>Cat cerebral arterial smooth muscle cells express cytochrome P450 4A2 enzyme and produce the vasoconstrictor 20-HETE which enhances L-type Ca2+ current</title><title>The Journal of physiology</title><addtitle>J Physiol</addtitle><description>Cerebral arteries express cytochrome P450 4A enzymes (P450 4A) and produce 20- hydroxyeicosatetraenoic acid (20-HETE), a potent
constrictor of pial arterioles. It is not known which cell type in the vessel wall is responsible for the formation of 20-HETE.
We examined whether freshly isolated cerebral arterial muscle cells (VSMCs) express P450 4A and produce 20-HETE. We also studied
the effect of 20-HETE on pressurized cerebral arteries and on whole-cell L-type Ca 2+ current ( I Ca ) recorded in cat cerebral VSMCs.
Cat cerebral VSMCs incubated with [ 14 C]arachidonic acid ([ 14 C]AA) produced 20-HETE (3.9 ± 1.1 pmol min â1 (mg protein) â1 ).
Reverse transcription-polymerase chain reaction studies revealed that cat cerebral VSMCs express mRNA for P450 4A which metabolizes
AA to 20-HETE. Cloning and sequencing of the cDNA amplified from mRNA isolated from VSMCs showed > 96% amino acid homology
to the rat and human P450 4A2 and 4A3.
20-HETE (1â300 n m ) induced a concentration-dependent constriction of cat cerebral arteries, which was inhibited by nifedipine.
Addition of 10 and 100 n m 20-HETE to the bath increased peak I Ca by 50 ± 3 and 100 ± 10%, respectively. This effect was not influenced by altering the frequency of depolarization. 20-HETE
(100 n m ) failed to increase I Ca in the presence of nifedipine.
These results demonstrate that cat cerebral VSMCs express P450 4A enzyme, and produce 20-HETE which activates L-type Ca 2+ channel current to promote cerebral vasoconstriction.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Arachidonic Acid - metabolism</subject><subject>Cats</subject><subject>Cerebral Arteries - metabolism</subject><subject>Cerebral Arteries - physiology</subject><subject>Cloning, Molecular</subject><subject>Cytochrome P-450 CYP4A</subject><subject>Cytochrome P-450 Enzyme System - biosynthesis</subject><subject>Cytochrome P-450 Enzyme System - chemistry</subject><subject>DNA Primers</subject><subject>Humans</subject><subject>Hydroxyeicosatetraenoic Acids - metabolism</subject><subject>Hydroxyeicosatetraenoic Acids - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Membrane Potentials - drug effects</subject><subject>Membrane Potentials - physiology</subject><subject>Mixed Function Oxygenases - biosynthesis</subject><subject>Mixed Function Oxygenases - chemistry</subject><subject>Molecular Sequence Data</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Muscle, Smooth, Vascular - physiology</subject><subject>Nifedipine - pharmacology</subject><subject>Original</subject><subject>Polymerase Chain Reaction</subject><subject>Rats</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Sequence Alignment</subject><subject>Sequence Homology, Amino Acid</subject><subject>Transcription, Genetic</subject><subject>Vasoconstriction - drug effects</subject><subject>Vasoconstriction - physiology</subject><subject>Vasoconstrictor Agents - pharmacology</subject><issn>0022-3751</issn><issn>1469-7793</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkV-L1DAUxYso6-zqRxDypA9La5r-S0CEZZh1lQH3YXwOaXq7ydA2NUl3pn4Rv66pMwyal9xwcs6B-4silOIkDefjPknzksVVxbIkZYwmVZXWLjm-iFYX4WW0wpiQOKuK9HV07dwe4zTDjF1FV6zAlGZ0Ff1eC48kWKit6JCwHqwOg-uN8Qr1k5MdBL3rHILjaME5JGdvpLKmB_SYFxjldwTB8GsObzE0aLSmmSQgrwA9C2ekGZy3WnpjEcHxw2a3QQelpQomJQYJDm1jP4-A1oLcIjlZC4N_E71qRefg7fm-iX7cb3brh3j7_cvX9d02VhnL05jUFFNGqWBl3pCKZqzGpYAWoKQtFAzXbdtACWVb5gUpSC2wKMq8rBlN67xtspvo8yl3nOoeGhmqwyL4aHUv7MyN0Px_ZdCKP5lnTkiGKWEh4P05wJqfEzjPe-2WhYkBzOR4xaq8JEURPr77t-lScUYR9E8n_aA7mC9yivlCnO_5ApYvYPlCnP8lzo989-0xjMH-4WRX-kkdtAU-qtlpEwBo8DMvcMWzxZT9ActVsHw</recordid><startdate>19980315</startdate><enddate>19980315</enddate><creator>Gebremedhin, Debebe</creator><creator>Lange, Andrew R.</creator><creator>Narayanan, Jayashree</creator><creator>Aebly, Mikael R.</creator><creator>Jacobs, Elizabeth R.</creator><creator>Harder, David R.</creator><general>The Physiological Society</general><general>Blackwell Science Ltd</general><general>Blackwell Science Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19980315</creationdate><title>Cat cerebral arterial smooth muscle cells express cytochrome P450 4A2 enzyme and produce the vasoconstrictor 20-HETE which enhances L-type Ca2+ current</title><author>Gebremedhin, Debebe ; Lange, Andrew R. ; Narayanan, Jayashree ; Aebly, Mikael R. ; Jacobs, Elizabeth R. ; Harder, David R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h3941-2b808988a964d27839b06aefee68fe590bffde6e6f645252ba0a5646b981b4fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Arachidonic Acid - metabolism</topic><topic>Cats</topic><topic>Cerebral Arteries - metabolism</topic><topic>Cerebral Arteries - physiology</topic><topic>Cloning, Molecular</topic><topic>Cytochrome P-450 CYP4A</topic><topic>Cytochrome P-450 Enzyme System - biosynthesis</topic><topic>Cytochrome P-450 Enzyme System - chemistry</topic><topic>DNA Primers</topic><topic>Humans</topic><topic>Hydroxyeicosatetraenoic Acids - metabolism</topic><topic>Hydroxyeicosatetraenoic Acids - pharmacology</topic><topic>In Vitro Techniques</topic><topic>Membrane Potentials - drug effects</topic><topic>Membrane Potentials - physiology</topic><topic>Mixed Function Oxygenases - biosynthesis</topic><topic>Mixed Function Oxygenases - chemistry</topic><topic>Molecular Sequence Data</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Muscle, Smooth, Vascular - physiology</topic><topic>Nifedipine - pharmacology</topic><topic>Original</topic><topic>Polymerase Chain Reaction</topic><topic>Rats</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Sequence Alignment</topic><topic>Sequence Homology, Amino Acid</topic><topic>Transcription, Genetic</topic><topic>Vasoconstriction - drug effects</topic><topic>Vasoconstriction - physiology</topic><topic>Vasoconstrictor Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gebremedhin, Debebe</creatorcontrib><creatorcontrib>Lange, Andrew R.</creatorcontrib><creatorcontrib>Narayanan, Jayashree</creatorcontrib><creatorcontrib>Aebly, Mikael R.</creatorcontrib><creatorcontrib>Jacobs, Elizabeth R.</creatorcontrib><creatorcontrib>Harder, David R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gebremedhin, Debebe</au><au>Lange, Andrew R.</au><au>Narayanan, Jayashree</au><au>Aebly, Mikael R.</au><au>Jacobs, Elizabeth R.</au><au>Harder, David R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cat cerebral arterial smooth muscle cells express cytochrome P450 4A2 enzyme and produce the vasoconstrictor 20-HETE which enhances L-type Ca2+ current</atitle><jtitle>The Journal of physiology</jtitle><addtitle>J Physiol</addtitle><date>1998-03-15</date><risdate>1998</risdate><volume>507</volume><issue>3</issue><spage>771</spage><epage>781</epage><pages>771-781</pages><issn>0022-3751</issn><eissn>1469-7793</eissn><abstract>Cerebral arteries express cytochrome P450 4A enzymes (P450 4A) and produce 20- hydroxyeicosatetraenoic acid (20-HETE), a potent
constrictor of pial arterioles. It is not known which cell type in the vessel wall is responsible for the formation of 20-HETE.
We examined whether freshly isolated cerebral arterial muscle cells (VSMCs) express P450 4A and produce 20-HETE. We also studied
the effect of 20-HETE on pressurized cerebral arteries and on whole-cell L-type Ca 2+ current ( I Ca ) recorded in cat cerebral VSMCs.
Cat cerebral VSMCs incubated with [ 14 C]arachidonic acid ([ 14 C]AA) produced 20-HETE (3.9 ± 1.1 pmol min â1 (mg protein) â1 ).
Reverse transcription-polymerase chain reaction studies revealed that cat cerebral VSMCs express mRNA for P450 4A which metabolizes
AA to 20-HETE. Cloning and sequencing of the cDNA amplified from mRNA isolated from VSMCs showed > 96% amino acid homology
to the rat and human P450 4A2 and 4A3.
20-HETE (1â300 n m ) induced a concentration-dependent constriction of cat cerebral arteries, which was inhibited by nifedipine.
Addition of 10 and 100 n m 20-HETE to the bath increased peak I Ca by 50 ± 3 and 100 ± 10%, respectively. This effect was not influenced by altering the frequency of depolarization. 20-HETE
(100 n m ) failed to increase I Ca in the presence of nifedipine.
These results demonstrate that cat cerebral VSMCs express P450 4A enzyme, and produce 20-HETE which activates L-type Ca 2+ channel current to promote cerebral vasoconstriction.</abstract><cop>Oxford, UK</cop><pub>The Physiological Society</pub><pmid>9508838</pmid><doi>10.1111/j.1469-7793.1998.771bs.x</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of physiology, 1998-03, Vol.507 (3), p.771-781 |
| issn | 0022-3751 1469-7793 |
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| source | MEDLINE; Wiley Online Library Free Content; Access via Wiley Online Library; IngentaConnect Free/Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Amino Acid Sequence Animals Arachidonic Acid - metabolism Cats Cerebral Arteries - metabolism Cerebral Arteries - physiology Cloning, Molecular Cytochrome P-450 CYP4A Cytochrome P-450 Enzyme System - biosynthesis Cytochrome P-450 Enzyme System - chemistry DNA Primers Humans Hydroxyeicosatetraenoic Acids - metabolism Hydroxyeicosatetraenoic Acids - pharmacology In Vitro Techniques Membrane Potentials - drug effects Membrane Potentials - physiology Mixed Function Oxygenases - biosynthesis Mixed Function Oxygenases - chemistry Molecular Sequence Data Muscle, Smooth, Vascular - metabolism Muscle, Smooth, Vascular - physiology Nifedipine - pharmacology Original Polymerase Chain Reaction Rats RNA, Messenger - biosynthesis Sequence Alignment Sequence Homology, Amino Acid Transcription, Genetic Vasoconstriction - drug effects Vasoconstriction - physiology Vasoconstrictor Agents - pharmacology |
| title | Cat cerebral arterial smooth muscle cells express cytochrome P450 4A2 enzyme and produce the vasoconstrictor 20-HETE which enhances L-type Ca2+ current |
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