Expression of 5-hydroxytryptamine receptor subtype messenger RNA in interstitial cells from human heart valves.
OBJECTIVE
Severe heart valve disorder has been reported in patients receiving a combination of the anorectic drugs fenfluramine and phentermine. The exact molecular mechanisms involved remain unknown. Fenfluramine alters the serotonin level in the brain, while phentermine interferes with the pulmonary clearance of serotonin; these data suggest that serotonin levels affect regulation of valve function. The aim of the present study was to characterize the serotonin receptor (5-hydroxytryptamine) subtypes expressed in the interstitial cells of human heart valves.


METHODS
Interstitial cells were isolated and cultured from the aortic, pulmonary, mitral and tricuspid valves of recipient hearts obtained during transplantation. Total RNA was extracted from cultured cells in order to determine 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 expressed in all four heart valves. This is significant as the 1B and 1D receptor 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 valves.


CONCLUSIONS
We conclude that preliminary evidence exists for the presence of distinct subsets of 5-HT receptors in human heart valves, indicating that interstitial cells of the valves potentially respond to serotonin levels.
Roy
A
A
Department of Cardiothoracic Surgery, Imperial College School of Medicine, National Heart and Lung Institute, Heart Science Centre, Harefield Hospital, Middlesex, UK.
Brand
N J
NJ
Yacoub
M H
MH
D001067:Appetite Depressants / Q000633:toxicity; D046508:Culture Techniques; D005109:Extracellular Matrix / Q000187:drug effects / Q000235:genetics*; D005277:Fenfluramine / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006351:Heart Valves / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D010645:Phentermine / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics*; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001067:Appetite Depressants; C470302:HTR1B protein, human; D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D005277:Fenfluramine; D010645:Phentermine