Comparison of the function of the serotonin transporter in the vasculature of male and female rats

Abstract

Summary The serotonin transporter (SERT) handles serotonin (5-hydroxytryptamine, 5-HT) and is blocked by the antidepressant SERT inhibitors fluoxetine and fluvoxamine. While the importance of SERT in the central nervous system is clear, SERT also functions in the peripheral vasculature. We tested the hypothesis that vasculature from female rats has increased SERT function compared to male rats because females are more responsive to SERT inhibitors.In addition to in vitro experiments, we imposed the challenge of a 5-HT infusion via mini-pump (7 days) to investigate how males vs females handle chronically elevated levels of 5-HT. The SERT knockout (KO) and wild type (WT) rat were used.Blood vessels from the female (aorta, carotid artery, jugular vein and vena cava) took up 5-HT acutely in vitro in a SERT-dependent fashion (measured by HPLC). In isometric contractility experiments using isolated tissue baths, SERT affected contractility as evidenced by the 8-fold increase in potency of 5-HT in fluvoxamine-incubated WT aortae compared to control; fluvoxamine did not alter 5-HT-induced contraction in aortae from the SERT KO female rat. Infusion of 5-HT resulted in an increase in tissue 5-HT that was reduced to a larger extent in blood vessels from the female vs male SERT KO rat. Contraction to 5-HT in aortae from 5-HT-infused SERT KO rats was abolished compared to SERT WT rats.Collectively, these data suggest that SERT function, when challenged with 5-HT, is modestly more important in the vasculature of the female vs male rat.

An immunohistochemical analysis of SERT in the blood–brain barrier of the male rat brain

“…Linder et al (2011) demonstrated a 50% decrease in the absolute magnitude of blood pressure fall to chronically infused 5-HT in both male and female SERT-knockout compared to wild type rats. While a serotonergic system, including SERT, exists in peripheral vasculature (Linder et al, 1008; Ni et al, 2006), it is difficult to imagine a mechanism whereby loss of SERT in the vasculature would reduce the ability of chronically infused 5-HT to decrease blood pressure.…”

Analysis of membrane transport mechanisms of endogenous substrates using chromatographic techniques

“…Most studies on the evaluation of serotonin transport via SLC6A3, SLC6A4/5‐HTT/SERT, SLC18A2 and SLC22A3 by chromatographic techniques have used HPLC–EC, usually with an octadecylsilyl (C 18 ) column (Table ). Serotonin has been determined in brain dialysates, cochlear supernatants, plasma and various tissues by HPLC–EC (Armando et al, ; Callaghan et al, ; Cedeño et al, ; Choi et al, ; Fazzino et al, ; Feng et al, ; Huff et al, ; Kim et al, ; Kish et al, ; Kreiss et al, ; Linder et al, , , ; Nakatani et al, ; Ni et al, ; Ni et al, ; Pazzagli et al, ; Reader et al, ; Ren‐Patterson et al, ; Sánchez et al, ; Taylor et al, ; Tsuruoka et al, ; Vicente‐Torres et al, ; Vogel et al, ; Wei et al, ; Zhang et al, ; Zhou et al, ) and by HPLC–FL (Huang et al, ). Fanzzino et al demonstrated serotonin determination in human monocytes and lymphocytes (Fazzino et al, ).…”

Serotonergic mechanisms of regulation of the systemic circulation vessels lumen

“…Кроме того, есть сведения о существовании систем синтеза, захвата, выделения и расщепления 5-HT клетками эндотелия артерий и вен [24]. По мнению авторов, проводивших исследование на генетически нокаутированных по SERT-генам крысах, указанная транспортная система предупреждает десенситизацию 5-HT 2 -рецепторов, сохраняя тем самым способность сосуда к вазоконстрикции [21].…”

“…Гладкие мышцы сосудистой стенки способны расслабляться вследствие активации 5-НТ 7 -рецепторов [8,30] -это результат прямого действия 5-HT. Вместе с тем 5-HT 1B/1D -, 5-HT 2A -рецепторы эндотелия и 5-HT 2B -рецепторы гладких мышц обеспечивают вазоконстрикцию [21,22].…”