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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1992-12-18
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pubmed:abstractText |
1. We investigated the potent 5-hydroxytryptamine (5-HT)-mediated vasorelaxation of the sheep pulmonary vein. Here we present evidence that this response is due to activation of 5-HT4 receptors. 2. 5-HT (1-1000 nM) caused concentration-dependent, maintained relaxations (pEC50 = 8.4 +/- 0.1) of isolated rings of sheep pulmonary vein pre-contracted with endothelin-1 (3 nM). 3. The relaxation response to 5-HT was unaffected by either removal of the endothelium or by inhibition of NO-synthase by NG-nitro-L-arginine (100 microM). 4. Ketanserin, methiothepin, methysergide and MDL 72222 at concentrations that selectively block 5-HT2, 5-HT1-like and 5-HT3 receptors respectively, had no effect on the concentration-relaxation curve to 5-HT. 5. ICS 205-930 (1-10 microM) competitively antagonized the concentration-relaxation curve to 5-HT with a pA2 of approximately 6.7. 6. Increasing the concentration of ICS 205-930 from 10 to 30 microM did not cause a further rightward shift of the 5-HT concentration-relaxation curve. The pEC50 of 6.50 for 5-HT in the presence of ICS 205-930 (30 microM) was taken as an estimate of the affinity of 5-HT for 5-HT1-like receptors since methiothepin (10 nM) unmasked further competitive inhibition of 5-HT in the presence of this concentration of ICS 205-930. 7. Other 5-HT agonists including 5-carboxamidotryptamine (5-CT), alpha-methyl-5-HT and BIMU 8 (but not 2-methyl-5-HT) also relaxed the pulmonary vein.The response to 5-CT was inhibited by methiothepin (10 nM) and methysergide (100 nM) but unaffected by ICS 205-930 (30 microM), whilst that toa-methyl-5-HT and BIMU 8 was unaffected by methiothepin (10 nM) but blocked by ICS 205-930(estimated pKB values of 6.4 and 6.9 respectively). Relaxation curves to both 5-HT and BIMU 8 were unaffected by cocaine (6 microM).8. In conclusion, these results indicate that the sheep pulmonary vein possesses 5-HT4 receptors that mediate potent endothelium-independent relaxation. 5-HT,-like relaxant receptors are also present in this tissue but 5-HT has a lower affinity at these receptors. This preparation may thus provide a robust and sensitive bioassay for future development of selective 5-HT4 receptor agonists and antagonists.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-1203621,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-13651579,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-1658664,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-1852778,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-1855122,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-1881455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-2043916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-2169944,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-2207493,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-2314390,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-2427147,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-2541857,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-2555720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-2652154,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-2849052,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-2850055,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-2875415,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-3350057,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-3607360,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-3839291,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-6288415,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-6621711,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-6662198,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1422600-7214093
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0007-1188
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
107
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
591-6
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:1422600-Animals,
pubmed-meshheading:1422600-Arginine,
pubmed-meshheading:1422600-Dose-Response Relationship, Drug,
pubmed-meshheading:1422600-Endothelium, Vascular,
pubmed-meshheading:1422600-Female,
pubmed-meshheading:1422600-Male,
pubmed-meshheading:1422600-Muscle, Smooth, Vascular,
pubmed-meshheading:1422600-Muscle Relaxation,
pubmed-meshheading:1422600-Nitroarginine,
pubmed-meshheading:1422600-Pulmonary Veins,
pubmed-meshheading:1422600-Receptors, Serotonin,
pubmed-meshheading:1422600-Serotonin,
pubmed-meshheading:1422600-Serotonin Antagonists,
pubmed-meshheading:1422600-Serotonin Receptor Agonists,
pubmed-meshheading:1422600-Sheep
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pubmed:year |
1992
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pubmed:articleTitle |
5-Hydroxytryptamine (5-HT) mediates potent relaxation in the sheep isolated pulmonary vein via activation of 5-HT4 receptors.
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pubmed:affiliation |
Baker Medical Research Institute, Prahran, Victoria, Australia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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