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5-Hydroxytryptamine (5HT) Receptors in the Heart Valves of Cynomolgus Monkeys and Sprague-Dawley Rats

Chandikumar S. Elangbam, Ruth M. Lightfoot, Lawrence W. Yoon, Donald R. Creech, Robert S. Geske, Christopher W. Crumbley, Lisa D. Gates and Henry G. Wall

Pathology (CSE,HGW,LDG), Safety Assessment (RML), Investigative Toxicology and Pathology (LWY,DRC), and Quantitative Expression and Genomic Histology (RSG,CWC), GlaxoSmithKline Inc., Research Triangle Park, North Carolina

Correspondence to: C.S. Elangbam, PhD, DACVP, DABT Director, Pathophysiology, Pathology Department, Room 9:3010, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709. E-mail: chandi.s.elangbam{at}gsk.com

5-Hydroxytryptamine-2B receptor (5HT2BR) stimulation is known to cause fibroblast mitogenesis, and the mitogenic effect has been proposed to trigger valvular heart disease in humans. In this study, we used real-time polymerase chain reaction (TaqMan) to quantify transcript levels of 5HT2B, 5HT2C, and 5HT1B receptors and immunohistochemistry (IHC) to detect the tissue localization of these receptors in the normal heart valves of cynomolgus (CM) monkeys and Sprague-Dawley (S-D) rats. In both species, positive immunostaining was noted for 5HT1B and 5HT2B receptors in mitral, tricuspid, aortic, and pulmonary valves, and the cell types showing positive staining were interstitial cells and endothelial cells lining the valve leaflet. In CM monkeys, 5HT2CR was expressed only in the endothelial cells lining the leaflet, whereas S-D valves were negative for this receptor. IHC results were correlated with 5HT2B and 5HT1B receptor transcripts for all four valves. However, 5HT2C receptor transcripts were lower than 5HT2B or 5HT1B in all CM monkey valves, whereas 5HT2C transcripts were below the level of detection in any of the S-D rat valves. Our data showed the expression of 5HT2B, 5HT1B, and 5HT2C receptors in the normal heart valves of CM monkeys and S-D rats, and IHC and TaqMan techniques may be used to study the potential mechanism of compounds with 5HT2BR agonist activity.

(J Histochem Cytochem 53:671–677, 2005)

Key Words: heart valve • 5-hydroxytryptamine (5HT) • receptor • immunohistochemistry • TaqMan • cynomolgus monkey • Sprague-Dawley rat

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