5-Hydroxytryptamine receptors in the human cardiovascular system

Kaumann, Alberto J.; Levy, Finn Olav

doi:10.1016/j.pharmthera.2005.12.004

Cited by 262 publications

(230 citation statements)

References 334 publications

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“…Phospholipase C (PLC) is known to couple with Gαq and mediate the intracellular signaling of 5‐HT2Rs 3. Thus, we pretreated SMCs with a PLC inhibitor, U73122, before the exposure to BW723C86.…”

Section: Resultsmentioning

confidence: 99%

“…A multitude of effects of 5‐HT have been demonstrated on the cardiovascular systems 3. Plasma levels of 5‐HT were increased in vascular remodeling diseases, such as PAH, hypertension, and atherosclerosis 12, 13, 76, 77.…”

Section: Discussionmentioning

confidence: 99%

“…Emerging evidence has suggested that the dysregulated serotonin system is implicated in the pathogeneses of several cardiovascular diseases. As an important vasoconstrictor, 5‐HT elicited hyperresponsiveness in hypertension, pulmonary arterial hypertension (PAH), and injured coronary arteries 2, 3, 4, 5, 6. 5‐HT also induced mitogenic response and was implicated in the remodeling of cardiovascular tissues, such as cardiac hypertrophy, fibrosis, valve hyperplasia,7 PAH, and hypertension 8.…”

Section: Introductionmentioning

confidence: 99%

“…The vascular effects of 5‐HT are mediated primarily by 5‐HT1 and 5‐HT2 receptors, which belong to the G‐protein–coupled receptor family 3. 5‐HT receptor 2B (5‐HT2BR) has a key role in the previously mentioned 5‐HT–related diseases, including cardiac hypertrophy, valve hyperplasia, and fibrosis 19, 20, 21.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of 5‐Hydroxytryptamine Receptor 2B Reduced Vascular Restenosis and Mitigated the β‐Arrestin2–Mammalian Target of Rapamycin/p70S6K Pathway

Liu

Wang

et al. 2018

JAHA

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BackgroundAs a monoamine neurotransmitter, 5‐hydroxytryptamine (5‐HT) or serotonin modulates mood, appetite, and sleep. Besides, 5‐HT also has important peripheral functions. 5‐HT receptor 2B (5‐HT2BR) plays a key role in cardiovascular diseases, such as pulmonary arterial hypertension and cardiac valve disease. Percutaneous intervention has been used to restore blood flow in occlusive vascular disease. However, restenosis remains a significant problem. Herein, we investigated the role of 5‐HT2BR in neointimal hyperplasia, a key pathological process in restenosis.Methods and ResultsThe expression of 5‐HT2BR was upregulated in wire‐injured mouse femoral arteries. In addition, BW723C86, a selective 5‐HT2BR agonist, promoted the injury response during restenosis. 5‐HT and BW723C86 stimulated migration and proliferation of rat aortic smooth muscle cells. Conversely, LY272015, a selective antagonist, attenuated the 5‐HT–induced smooth muscle cell migration and proliferation. In vitro study showed that the promigratory effects of 5‐HT2BR were mediated through the activation of mammalian target of rapamycin (mTOR)/p70S6K signaling in a β‐arrestin2–dependent manner. Inhibition of mammalian target of rapamycin or p70S6K mitigated 5‐HT2BR–mediated smooth muscle cell migration. Mice with deficiency of 5‐HT2BR showed significantly reduced neointimal formation in wire‐injured arteries.ConclusionsThese results demonstrated that activation of 5‐HT2BR and β‐arrestin2–biased downstream signaling are key pathological processes in neointimal formation, and 5‐HT2BR may be a potential target for the therapeutic intervention of vascular restenosis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of 5‐Hydroxytryptamine Receptor 2B Reduced Vascular Restenosis and Mitigated the β‐Arrestin2–Mammalian Target of Rapamycin/p70S6K Pathway

Liu

Wang

et al. 2018

JAHA

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“…Several 5-HT 4 receptor splice variants are expressed in human heart but functional differences have not yet been detected (Reviewed in Kaumann and Levy 2006). 5-HT does not only increase myocardial force and hasten relaxation Sanders and Kaumann 1992;Brattelid et al 2004), but can also elicit arrhythmic contractions in atrial trabeculae (Kaumann and Sanders 1994) and myocytes (Sanders et al 1995) as well as in ventricular trabeculae (Brattelid et al 2004).…”

mentioning

confidence: 99%

Surprises from a cardiac 5-HT4 TG mouse: spontaneous atrial arrhythmias by endogenous 5-HT of atrial origin? Different mechanism of arrhythmias through 5-HT4 receptors and β-adrenoceptors?

Kaumann

2013

Naunyn-Schmiedeberg's Arch Pharmacol

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5-HT 4 receptors of human myocardium mediate cardiostimulant effects of 5-hydroxytryptamine (5-HT, serotonin) mainly through the G s protein→cAMP→PKA pathway. Several 5-HT 4 receptor splice variants are expressed in human heart but functional differences have not yet been detected (Reviewed in Kaumann and Levy 2006). 5-HT does not only increase myocardial force and hasten relaxation Sanders and Kaumann 1992;Brattelid et al. 2004), but can also elicit arrhythmic contractions in atrial trabeculae (Kaumann and Sanders 1994) and myocytes (Sanders et al. 1995) as well as in ventricular trabeculae (Brattelid et al. 2004). It has been proposed that 5-HT can initiate atrial fibrillation (Kaumann 1994) and facilitate arrhythmias in patients with ischaemic heart disease (Brattelid et al. 2004). Chronic treatment of patients with β-blockers potentiates the inotropic effects of 5-HT in atrial trabeculae and myocytes (Sanders et al. 1995). 5-HT increases the L-type Ca 2+ current (I Ca,L )in human atrial myocytes in a PKA-dependent manner (Ouadid et al. 1992). Chronic treatment of patients with β-blockers potentiates the effects of 5-HT on I Ca,L and arrhythmic activity of atrial myocytes (Pau et al. 2003). 5-HT causes also cardiostimulation in porcine heart (Kaumann 1990;Parker et al. 1994;Brattelid et al. 2004), but not in other non-primate species, at least under physiological conditions. Arrhythmias, probably mediated through 5-HT 4 receptors, have also been reported in porcine atrium (Rahme et al. 1999). Rat ventricular 5-HT 4 receptor expression and function is induced in rats with ischaemic heart failure but not in normal rats (Qvigstad et al. 2005), plausibly by reactivating a phenotype resembling late foetal development (Brattelid et al. 2012).Gergs et al. (2010) overexpressed human 5-HT 4a receptors in the heart of mice that normally do not express functional cardiac 5-HT 4 receptors. In these transgenic mice 5-HT produced sinoatrial tachycardia, increases in ventricular I Ca,L and Ca 2+ transients, positive inotropic and lusitropic effects in ventricle, associated with phosphorylation of phospholamban (PLB) at Ser16 in ventricular myocytes and Thr 17 in perfused working hearts. These features resemble the pharmacology of 5-HT 4 receptors in human heart. 5-HT, but hardly isoprenaline, also caused arrhythmic Ca 2+ transients in venricular myocytes from TG hearts. Interesting, in isolated hearts from these TG hearts Gergs et al. (2010) demonstrated episodes of spontaneous polymorphic atrial arrhythmias in the absence of exogenous 5-HT that resemble shortlasting episodes of atrial fibrillation.In an additional report of Gergs et al. (2013) in the present issue of Naunyn-Schmiedeberg's Archives of Pharmacology, the authors studied the effects of 5-HT on paced left atria and spontaneously beating right atria from their TG mouse. As expected, 5-HT produced sinoatrial tachycardia and increases in left atrial force, left atrial arrhythmias, phosphorylation of PLB at Ser16 and arrhythmias, which were antagonised by 5-HT 4 re...

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Serotonin

Bäder¹

2008

Cardiovascular Hormone Systems

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5-Hydroxytryptamine receptors in the human cardiovascular system

Cited by 262 publications

References 334 publications

Inhibition of 5‐Hydroxytryptamine Receptor 2B Reduced Vascular Restenosis and Mitigated the β‐Arrestin2–Mammalian Target of Rapamycin/p70S6K Pathway

Inhibition of 5‐Hydroxytryptamine Receptor 2B Reduced Vascular Restenosis and Mitigated the β‐Arrestin2–Mammalian Target of Rapamycin/p70S6K Pathway

Surprises from a cardiac 5-HT4 TG mouse: spontaneous atrial arrhythmias by endogenous 5-HT of atrial origin? Different mechanism of arrhythmias through 5-HT4 receptors and β-adrenoceptors?

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