Distribution of 5-HT(1B), 5-HT(1D) and 5-HT(1F) receptor expression in rat trigeminal and dorsal root ganglia neurons: relevance to the selective anti-migraine effect of triptans.
Triptans, acting as serotonin, 5-HT(1B/1D/1F), receptor agonists, provide an effective and established treatment option in migraine and cluster headache. Clinical observations suggest a relatively specific effect of these compounds on primary headache disorders, but not in other pain syndromes. The mechanism of this specificity, however, is not well understood. Hence, we systematically studied primary sensory ganglia in rat to determine if the peripheral distribution of 5HT(1B/1D/1F) receptors showed any anatomical difference that would account for the specificity of clinical effect. Rat primary afferent and sensory ganglia neurons--trigeminal ganglia (Vg), and dorsal root ganglia (DRG): C(2), C(5), T(5), L(5)--were examined using paraffin-embedded, slide-bound tissue sections reacted with specific primary antibodies for rat 5-HT(1B, 1D) and (1F) receptors in a peroxidase-based immunohistochemical method. Immunoreactivity specific for all three serotonergic receptor subtypes was demonstrated in the five peripheral nervous system regions examined and quantitated. There was a good agreement for 5-HT(1B) and 5-HT(1D) receptors to that previously demonstrated in Vg and DRG L(5), while this was the first characterisation for 5-HT(1F) receptor in any of the five regions, as well as for 5-HT(1B) and 5HT(1D) receptors in DRG C(2), C(5) and T(5). In summary, all three 5-HT receptors are equally represented in Vg and the DRGs examined. We conclude that the triptans are theoretically able to bind to receptors at each level of the peripheral neuraxis without any apparent anatomical preference for the head.
Classey
J D
JD
Headache Group-Department of Neurology, University of California, San Francisco, CA 94115, USA.
Bartsch
T
T
Goadsby
P J
PJ
D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000166:cytology / Q000378:metabolism*; D014363:Tryptamines / Q000494:pharmacology*; D000096642:Receptor, Serotonin, 5-HT1F
D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D000096642:Receptor, Serotonin, 5-HT1F