Expression of 5-hydroxytryptamine receptor subtype messenger RNA in interstitial cells from human heart valve

Background and aim of the study: Severe heart valve disorder has been repor ted in patients receiving a combination of the anorectic drugs fenfluramine and phentermine. The exact molecular mechanisms involved remain unknown. F enfluramine alters the serotonin level in the brain, while phentermine inte rferes with the pulmonary clearance of serotonin; these data suggest that s erotonin levels affect regulation of valve function. The aim of the present study was to characterize the serotonin receptor (5-hydroxytryptamine) sub types expressed in the interstitial cells of human heart valves. Methods: Interstitial cells were isolated and cultured from the aortic, pul monary, mitral and tricuspid valves of recipient hearts obtained during tra nsplantation. Total RNA was extracted from cultured cells in order to deter mine gene expression by reverse transcription-polymerase chain reaction (RT -PCR) using 5-hydroxytryptamine (5-HT) subtype-specific primer pairs. Results: The results show that: (i) 5-HT 1B and 1D receptor subtypes are ex pressed in all four heart valves. This is significant as the 1B and 1D rece ptor subfamilies are the target of the anti-migraine drug sumatriptan, and these receptors regulate cardiac function and movement; (ii) 5-HT 1A, 5-HT 1E and 5-HT 1F are not expressed in interstitial cells isolated from the va lves. Conclusion: We conclude that preliminary evidence exists for the presence o f distinct subsets of 5-HT receptors in human heart valves, indicating that interstitial cells of the valves potentially respond to serotonin levels.