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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

5-Hydroxytryptamine (5-HT) mediates potent relaxation in the sheep isolated pulmonary vein via activation of 5-HT4 receptors.

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.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


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