Pharmacological characterization of the serotonin receptor mediating contraction in the rat jugular vein

Abstract

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.