Effects of sumatriptan on rat medullary dorsal horn neurons.
This study examined the cellular actions of the anti-migraine drug sumatriptan, on neurons in the substantia gelatinosa of the spinal trigeminal nucleus pars caudalis. Sumatriptan inhibited the miniature EPSC (mEPSC) rate in a dose dependent fashion, with an EC(50) of 250 nM. Sumatriptan (3 microM) inhibited the mEPSC rate by 36%, without altering the mEPSC amplitude. This effect was partially reversed by the 5HT(1D) specific antagonist BRL15572 (10 microM). In contrast, the 5HT(1B) agonist CP93129 (10 microm) did not alter the mEPSC rate. Furthermore, sumatriptan (3 microM) decreased the amplitude of electrically evoked EPSCs (eEPSC) by 40%. After incubating the slices in ketanserin (an antagonist which shows selectivity for 5HT(1D) over 5HT(1B) receptors) sumatriptan had little effect on eEPSC amplitude. In control conditions paired stimuli resulted in paired pulse depression (PPD; the ratio eEPSC(2)/eEPSC(1)=0.7+/-0.01), whilst in the presence of sumatriptan the PPD was blocked (ratio eEPSC(2)/eEPSC(1)=0.9+/-0.1). Sumatriptan produced no post-synaptic membrane current and had no significant effect on membrane conductance over a range of membrane potentials (-60 to -130 mV). RT-PCR experiments revealed the presence of mRNA for both 5HT(1D) and 5HT(1B) receptor subtypes in the trigeminal ganglia and subnucleus caudalis. These data suggest that sumatriptan acts pre-synaptically on trigeminal primary afferent central terminals to reduce the probability of release of glutamate, and that this action is mediated through 5HT(1D) receptors.
Jennings
E A
EA
Department Pharmacology, University of Sydney, Sydney, NSW 2006, Australia. e.jennings@unimelb.edu.au
Ryan
R M
RM
Christie
M J
MJ
D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics; D044346:Receptor, Serotonin, 5-HT1D / Q000235:genetics; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013376:Substantia Gelatinosa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018170:Sumatriptan / Q000494:pharmacology*; D014275:Trigeminal Caudal Nucleus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D017366:Serotonin Receptor Agonists; D018170:Sumatriptan