Bradykinin excites rat sympathetic neurons by inhibition of M current through a mechanism involving B2 receptors and G alpha q/11
Bradykinin (BK) is a peptide mediator released in inflammation that potently excites sympathetic neurons. We have studied the mechanism of this excitation in dissociated rat sympathetic neurons and found that at low nanomolar (EC50 = 0.9 nM) concentrations, BK inhibited the M-type K+ current IK(M)....
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| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 1995-02, Vol.14 (2), p.399-405 |
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| container_title | Neuron (Cambridge, Mass.) |
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| creator | Jones, S Brown, D A Milligan, G Willer, E Buckley, N J Caulfield, M P |
| description | Bradykinin (BK) is a peptide mediator released in inflammation that potently excites sympathetic neurons. We have studied the mechanism of this excitation in dissociated rat sympathetic neurons and found that at low nanomolar (EC50 = 0.9 nM) concentrations, BK inhibited the M-type K+ current IK(M). Studies with the selective antagonist Hoe140 revealed that this effect was mediated via the B2 receptor subtype, and mRNA encoding this receptor was identified in these neurons by RT-PCR. IK(M) inhibition was unaffected by Pertussis toxin or microinjection of antibodies to G alpha o but was selectively inhibited by microinjection of antibodies to G alpha q/11. Thus, BK is the most potent M current inhibitor yet described in mammalian neurons, and BK inhibition of M current is mediated by a G protein pathway similar to that activated by muscarinic acetylcholine receptors. |
| doi_str_mv | 10.1016/0896-6273(95)90295-3 |
| format | Article |
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We have studied the mechanism of this excitation in dissociated rat sympathetic neurons and found that at low nanomolar (EC50 = 0.9 nM) concentrations, BK inhibited the M-type K+ current IK(M). Studies with the selective antagonist Hoe140 revealed that this effect was mediated via the B2 receptor subtype, and mRNA encoding this receptor was identified in these neurons by RT-PCR. IK(M) inhibition was unaffected by Pertussis toxin or microinjection of antibodies to G alpha o but was selectively inhibited by microinjection of antibodies to G alpha q/11. Thus, BK is the most potent M current inhibitor yet described in mammalian neurons, and BK inhibition of M current is mediated by a G protein pathway similar to that activated by muscarinic acetylcholine receptors.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Bradykinin - analogs & derivatives</subject><subject>Bradykinin - antagonists & inhibitors</subject><subject>Bradykinin - pharmacology</subject><subject>Cells, Cultured</subject><subject>DNA Primers</subject><subject>Exons</subject><subject>GTP-Binding Proteins - physiology</subject><subject>Molecular Sequence Data</subject><subject>Neurons - drug effects</subject><subject>Neurons - physiology</subject><subject>Polymerase Chain Reaction</subject><subject>Potassium Channel Blockers</subject><subject>Potassium Channels - pharmacology</subject><subject>Rats</subject><subject>Receptors, Bradykinin - biosynthesis</subject><subject>Receptors, Bradykinin - physiology</subject><subject>RNA, Messenger - analysis</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Superior Cervical Ganglion - physiology</subject><issn>0896-6273</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kMFO3DAURb0oogP0D1rprap2kY4dJ0687CAKSIPY0LXlOC_ENLEztoM6y_55M8yI1ZOuzr3SO4R8ZvQHo0ysaS1FJvKKf5Pld0lzWWb8A1m9xx_JRYwvlLKilOycnFd1WYmiWpF_m6Db_R_rrAP8a2zCCEEniPtx0qnHZA04nIN3EZo9WNfbxibrHfgOHsDMIaBLkPrg5-ceNIxoeu1sHBf21Q-v1j3DJoeABqfkQwTtWrgFPUy9ht2asSty1ukh4qfTvSS_f908Xd9l28fb--uf28zkgvOsK1tKueCsKTQWsmhrwRrR5S3rWFM3klaU5nXRlBUaI43JNVueZJpy5KZAxi_J1-PuFPxuxpjUaKPBYdAO_RxVVS1ycioWsDiCJvgYA3ZqCnbUYa8YVQfb6qBVHbQqWao324ovtS-n_bkZsX0vnVTz_2gZfbE</recordid><startdate>199502</startdate><enddate>199502</enddate><creator>Jones, S</creator><creator>Brown, D A</creator><creator>Milligan, G</creator><creator>Willer, E</creator><creator>Buckley, N J</creator><creator>Caulfield, M P</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>199502</creationdate><title>Bradykinin excites rat sympathetic neurons by inhibition of M current through a mechanism involving B2 receptors and G alpha q/11</title><author>Jones, S ; Brown, D A ; Milligan, G ; Willer, E ; Buckley, N J ; Caulfield, M P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2633-f5d003631b4ae494d861b6f2d1f1b8b90700284b57ecc9cc2a17851a03e3c4e13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>Bradykinin - analogs & derivatives</topic><topic>Bradykinin - antagonists & inhibitors</topic><topic>Bradykinin - pharmacology</topic><topic>Cells, Cultured</topic><topic>DNA Primers</topic><topic>Exons</topic><topic>GTP-Binding Proteins - physiology</topic><topic>Molecular Sequence Data</topic><topic>Neurons - drug effects</topic><topic>Neurons - physiology</topic><topic>Polymerase Chain Reaction</topic><topic>Potassium Channel Blockers</topic><topic>Potassium Channels - pharmacology</topic><topic>Rats</topic><topic>Receptors, Bradykinin - biosynthesis</topic><topic>Receptors, Bradykinin - physiology</topic><topic>RNA, Messenger - analysis</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Superior Cervical Ganglion - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jones, S</creatorcontrib><creatorcontrib>Brown, D A</creatorcontrib><creatorcontrib>Milligan, G</creatorcontrib><creatorcontrib>Willer, E</creatorcontrib><creatorcontrib>Buckley, N J</creatorcontrib><creatorcontrib>Caulfield, M P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Neuron (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jones, S</au><au>Brown, D A</au><au>Milligan, G</au><au>Willer, E</au><au>Buckley, N J</au><au>Caulfield, M P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bradykinin excites rat sympathetic neurons by inhibition of M current through a mechanism involving B2 receptors and G alpha q/11</atitle><jtitle>Neuron (Cambridge, Mass.)</jtitle><addtitle>Neuron</addtitle><date>1995-02</date><risdate>1995</risdate><volume>14</volume><issue>2</issue><spage>399</spage><epage>405</epage><pages>399-405</pages><issn>0896-6273</issn><abstract>Bradykinin (BK) is a peptide mediator released in inflammation that potently excites sympathetic neurons. We have studied the mechanism of this excitation in dissociated rat sympathetic neurons and found that at low nanomolar (EC50 = 0.9 nM) concentrations, BK inhibited the M-type K+ current IK(M). Studies with the selective antagonist Hoe140 revealed that this effect was mediated via the B2 receptor subtype, and mRNA encoding this receptor was identified in these neurons by RT-PCR. IK(M) inhibition was unaffected by Pertussis toxin or microinjection of antibodies to G alpha o but was selectively inhibited by microinjection of antibodies to G alpha q/11. Thus, BK is the most potent M current inhibitor yet described in mammalian neurons, and BK inhibition of M current is mediated by a G protein pathway similar to that activated by muscarinic acetylcholine receptors.</abstract><cop>United States</cop><pmid>7857647</pmid><doi>10.1016/0896-6273(95)90295-3</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Neuron (Cambridge, Mass.), 1995-02, Vol.14 (2), p.399-405 |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Base Sequence Bradykinin - analogs & derivatives Bradykinin - antagonists & inhibitors Bradykinin - pharmacology Cells, Cultured DNA Primers Exons GTP-Binding Proteins - physiology Molecular Sequence Data Neurons - drug effects Neurons - physiology Polymerase Chain Reaction Potassium Channel Blockers Potassium Channels - pharmacology Rats Receptors, Bradykinin - biosynthesis Receptors, Bradykinin - physiology RNA, Messenger - analysis RNA, Messenger - biosynthesis Superior Cervical Ganglion - physiology |
| title | Bradykinin excites rat sympathetic neurons by inhibition of M current through a mechanism involving B2 receptors and G alpha q/11 |
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