Inhibition by 5-hydroxytryptamine and noradrenaline in substantia gelatinosa of guinea-pig spinal trigeminal nucleus.
1. Whole-cell and intracellular recordings were made from neurons in slices of guinea-pig spinal trigeminal nucleus pars caudalis. 2. 5-Hydroxytryptamine (5-HT) hyperpolarized 70% of neurons by activating 5-HT1A receptors. The effect was mimicked by 5-carboxamidotryptamine (5-CT) and (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronapthalene hydrobromide (8-OH-DPAT) and antagonized by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)-butyl]-piperazine hydrobromide (NAN 190) and pindobind-5-HT1A. Nine per cent of the neurons were depolarized by 5-HT. 3. In about 20% of recordings, 5-HT also evoked repetitive inhibitory postsynaptic potentials that were mediated by glycine. 4. Noradrenaline (NA) hyperpolarized 71% of neurons. This effect was mediated by activation of alpha 2-adrenoceptors, since 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK14304) also caused a hyperpolarization and idazoxan (1 microM) blocked the hyperpolarization to both NA and UK14304. Phenylephrine depolarized a subset of neurons and this depolarization was blocked by prazosin, suggesting an action mediated by activation of alpha 1-adrenoceptors. 5. NA also evoked repetitive GABAA-mediated inhibitory postsynaptic potentials in about 20% of recordings. The increase in synaptic activity was mimicked by phenylephrine and blocked by prazosin. 6. These results indicate that there are at least two mechanisms through which 5-HT and NA inhibit neurons: (i) in many cells both 5-HT and NA mediate a hyperpolarization through an increase of a potassium conductance; (ii) 5-HT and NA also activated GABA- and glycine-containing interneurons to cause IPSPs in separate groups of cells.
Grudt
T J
TJ
Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
Williams
J T
JT
Travagli
R A
RA
D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000818:Animals; D000068438:Brimonidine Tartrate; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013376:Substantia Gelatinosa / Q000166:cytology / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects; D014279:Trigeminal Nucleus, Spinal / Q000166:cytology / Q000187:drug effects*
D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D015221:Potassium Channels; D011810:Quinoxalines; D011963:Receptors, GABA-A; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D000068438:Brimonidine Tartrate; D009638:Norepinephrine