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 toward 5-HT receptor subtypes. We hypothesized that, as for other blood vessels, the 5-HT 1B/1D and 5-HT 2B receptor subtypes mediate contraction in RJV alongside the 5-HT 2A 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-HT 1A and the mixed 5-HT 1A/1B receptor agonists (Ϯ)-2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronapthalene (8-OH-DPAT) and 5-methoxy-3 (1,2,3,6-tetrahydropyridin-4-yl) (1H indole) (RU24969) caused contractions that were antagonized Serotonin (5-hydroxytryptamine; 5-HT) was first described as a substance with the ability to increase smooth muscle tone (Vialli and Erspamer, 1937;Rapport et al., 1948). 5-HT is synthesized by the enterochromaffin cells and released into the circulation. In the periphery, platelets are the largest store for 5-HT. It is interesting that our laboratory recently showed that peripheral vasculature has the ability to synthesize, take up, and metabolize 5-HT (Linder et al., 2008;. Moreover, the amount of 5-HT measured in veins is comparatively higher than in arteries, suggesting that peripheral veins also may constitute important stores of the amine (Linder et al., 2008). Thus, by controlling the amount of 5-HT within the peripheral vasculature environment, veins may exert relevant roles in adjusting vascular tone.

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The purpose of this study was to characterize pharmacologically the serotonin (5‐hydroxytryptamine; 5‐HT) receptors mediating contraction in the rat jugular vein (RJV). We hypothesized that 5‐HT2A receptor is not the only receptor mediating contraction in RJV. Endothelium‐intact rings of RJV were placed in a tissue bath for measurement of isometric contractile force induced by cumulative addition of agonists (1nM to 10 μM). The contractions induced by the 5‐HT1A/1B and 5‐HT1A receptor agonists, RU 24969 (pD2=‐log EC50 [M]=6.4±0.05) and 8‐OH‐DPAT (pD2=5.5±0.07), respectively, were not as robust as that induced by 5‐HT (pD2=6.8±0.17). The 5‐HT1B/1D/1F agonist sumatriptan failed to induce contraction. The 5‐HT2A receptor agonist DOI (pD2=7.78±0.12) was more potent, whereas the 5‐HT2B receptor agonist BW723C86 was less potent (pD2=6.17±0.12) when compared to the contraction induced by 5‐HT. The antagonists with high affinity for the 5‐HT2A and 5‐HT2B receptors, ketanserin (30nM) and LY266097 (10nM), respectively, caused a right‐shift of 5‐HT‐induced contraction. The 5‐HT1B/1D receptor antagonist GR127935 (10nM) had no effect on 5‐HT‐induced contraction. We conclude that 5‐HT‐induced contraction of RJV is mediated primarily by 5‐HT2A receptor. The involvement of 5‐HT2B and 5‐HT1A receptor subtypes can not be ruled out and deserve further investigation. By identifying receptor mechanisms, we can better understand how the newly discovered serotonergic system in veins may locally modify contraction.