Serotonin Receptors in Rat Jugular Vein: Presence and Involvement in the Contraction

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 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.

Evidence of active regulation of cerebral venous tone in individuals undergoing embolization of brain arteriovenous malformations

“…Both adrenergic and serotonergic regulation may be implicated, because recent immunohistochemical and ultrastructural data have confirmed the presence of serotonergic nerve terminals in the cerebral vein of Galen in rats (33). Furthermore, physiological studies have shown that serotonin-induced constriction of the rat jugular vein is mediated through 5-HT 2A , and to a lesser extent, 5-HT 2B receptors (17). Along with the neurogenic pathway, the endotheliumdependent pathway may be also implicated in the constriction of cerebral veins in response to blood flow reduction.…”

“…This model described venous blood flow from collapsible bridging veins subjected to varying levels of intracranial pressure to unyielding sinuses (22). Until recently, the indirect evidence for active cerebral venous regulation mostly stemmed from histochemical studies showing the presence of aminergic nerve endings in the venous wall (9,14,23), as well as from in vitro studies demonstrating venous wall responses to certain agonists (13,17). In addition, a recent study on healthy volunteers has also demonstrated an active response of intracranial cerebral veins during the overshoot phase of the Valsalva maneuver (30).…”

Involvement of Extracellular Signal-Regulated Kinase 5 in Kinin B1 Receptor Upregulation in Isolated Human Umbilical Veins

“…RNA isolation, cDNA synthesis, and quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) were performed as described in the online Supplemental Material and described by Linder et al (2010) and Fukushima et al (2014).…”