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(Circulation Research. 2004;94:1152.)
© 2004 American Heart Association, Inc.

Editorials

The Serotonin Transporter

A Vehicle to Elucidate Pulmonary Hypertension?

E. Kenneth Weir, Zhigang Hong, Anthony Varghese

From the Department of Medicine, VA Medical Center and the University of Minnesota, Minneapolis, Minn.

Correspondence to E. Kenneth Weir, MD, VA Medical Center (111C), One Veteran Drive, Minneapolis, MN 55417. E-mail weirx002@umn.edu

Key Words: membrane transport proteins • hypertension, pulmonary • transforming growth factor-ß • potassium channels

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Primary pulmonary hypertension (PPH) is a life-threatening disease that mostly affects young adults, more commonly women than men. It is characterized by vasoconstriction of the small pulmonary arteries, proliferation in all layers of the vessel wall, thrombosis-in situ, and inflammation. Serotonin (5-hydroxytryptamine, 5-HT) is thought to play a role in the pathogenesis of PPH, in part, because it is a pulmonary vasoconstrictor¹ and smooth muscle mitogen.^2,3 It is synthesized from L-tryptophan, primarily in the enterochromaffin cells of the small intestine. In the blood, 5-HT is mainly transported in the platelets, some are bound to plasma proteins, and only nanomolar concentrations are free in the plasma. The importance of the lungs in the removal of 5-HT from the blood has been known for more than 50 years.⁴ As much as 95% may be taken up or inactivated.⁵ 5-HT is taken up by the 5-HT transporter (5-HTT) in several cells including platelets, neurons, and pulmonary artery smooth muscle and endothelial cells. 5-HTT belongs to a large 12 transmembrane–domain gene family including the norepinephine transporter, glucose transporters, and transporters of other neurotransmitters. The amino acid sequence of cloned human 5-HTT reveals 6 putative phosphorylation sites, targets for PKA and PKC, which may activate 5-HTT. The Figure shows some of the cellular signaling pathways involving 5-HTT and 5-HT receptors.

View larger version (29K): [in this window] [in a new window]   Schematic representation of serotonin (5-HT) signaling pathways in pulmonary artery smooth muscle cells (PASMCs). Activation of serotonin receptors 5-HT1B, 5-HT2A, and 5-HT2B cause vasoconstriction, although 5-HT2B is also implicated in the mitogenic . . . [Full Text of this Article]

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				S. Jain, H. Ventura, and B. deBoisblanc Pathophysiology of Pulmonary Arterial Hypertension Seminars in Cardiothoracic and Vascular Anesthesia, June 1, 2007; 11(2): 104 - 109. [Abstract] [PDF]

				A. Varghese, Z. Hong, and E. K. Weir Serotonin-Induced Inhibition of KV Current: A Supporting Role in Pulmonary Vasoconstriction? Circ. Res., April 14, 2006; 98(7): 860 - 862. [Full Text] [PDF]