Selective 5-HT1D alpha serotonin receptor gene expression in trigeminal ganglia: implications for antimigraine drug development.
Pharmacological data suggest that the actions of antimigraine drugs such as sumatriptan may be mediated by 5-HT1D-like serotonin receptors on trigeminovascular nerve endings. We sought molecular evidence for the expression of an mRNA species encoding the 5-HT1D receptor subtype in guinea pig and human trigeminal ganglia, using the polymerase chain reaction with oligonucleotides uniquely homologous to the coding sequences of the 5-HT1B/D family (human 5-HT1D alpha and 5-HT1D beta; rat 5-HT1B). A single band of predicted size was observed in samples from guinea pig trigeminal ganglia; sequence analysis revealed the presence of a single message, which was 85% and 71% identical to the human 5-HT1D alpha and 5-HT1D beta receptor DNA sequences, respectively. Similar analyses of postmortem human trigeminal ganglia revealed the presence of 5-HT1D alpha, but not 5-HT1D beta, receptor message. Inasmuch as one recent report found that mRNA encoding only the 5-HT1D beta receptor subtype was expressed by vascular smooth muscle of the central nervous system, the present findings suggest the importance of developing selective 5-HT1D alpha receptor agonists as a strategy to reduce the risk of myocardial infarction and possibly stroke that complicates the acute treatment of migraine headache.
Rebeck
G W
GW
Neurology Service, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Maynard
K I
KI
Hyman
B T
BT
Moskowitz
M A
MA
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000503:physiopathology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D011985:Receptors, Serotonin / Q000145:classification / Q000235:genetics*; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D012668:Trigeminal Ganglion / Q000502:physiology*
D017931:DNA Primers; D012333:RNA, Messenger; D011985:Receptors, Serotonin