Abstract
Serotonin (5-hydroxytryptamine; 5-HT) is released during platelet aggregation, a phenomenon commonly observed in blood clot formation and venous diseases. Once released, 5-HT can interact with its receptors in the peripheral vasculature to modify vascular tone. The goal of this study was to perform a detailed pharmacological characterization of the 5-HT receptors involved in the contractile response of the rat jugular vein (RJV) using recently developed drugs with greater selectivity towards 5-HT receptor subtypes. We hypothesized that, as for other blood vessels, the 5-HT1B/1D and 5-HT2B receptor subtypes mediate contraction in RJV alongside the 5-HT2A receptor subtype. Endothelium-intact RJV rings were set up in an isolated organ bath for isometric tension recordings and contractile concentration-effect curves were obtained for 13 distinct serotonergic receptor agonists. Surprisingly, the 5-HT1A and the mixed 5-HT1A/1B receptor agonists 8-OH-DPAT and RU24969 caused contractions that were antagonized by the 5-HT1A receptor antagonist WAY100135. The contractile curve to 5-HT was shifted to the right by WAY100135, ketanserin (5-HT2A/C receptor antagonist) and LY266097 (5-HT2B receptor antagonist). Ketanserin also caused rightward shifts of the contractile curves to 8-OH-DPAT, RU24969 and the 5-HT2B receptor agonist BW723C86. Agonists for 5-HT1B/1D/1F, 5-HT3, 5-HT6 and 5-HT7 receptors were inactive. In real time PCR experiments that have never been performed in this tissue previously, we observed mRNA expression for the 5-HT2A, 5-HT2B and 5-HT7 receptors, whereas no significant mRNA expression was found for 5-HT1A, 5-HT1B and 5-HT1D receptors. These results support the 5-HT2A receptor as the main subtype targeted by 5-HT to contract the RJV.
Footnotes
- Received October 26, 2009.
- Revision received April 5, 2010.
- Accepted April 7, 2010.
- The American Society for Pharmacology and Experimental Therapeutics