5-HT2 and 5-HT3 receptors mediate two distinct depolarizing responses in rat dorsal root ganglion neurons.
The effects of serotonin (5-HT) were studied on transmembrane potentials in 188 rat dorsal root ganglion cells (150 A-type, 16 C-type and 22 unidentified neurons). 5-HT produced a concentration-dependent depolarization in 88% of these neurons. Membrane input resistance (Rin), determined from the slope of current-voltage displacement curves, was increased in 51% and decreased in 41% of the responding neurons. Both responses occurred in 8% of the neurons. No differences in these responses were observed between A- and C-type neurons. Norepinephrine (NE) depolarized 75% (n = 20) of the neurons tested while increasing the Rin. In cells where 5-HT decreased Rin, 2-methyl 5-HT, but not alpha-methyl 5-HT, mimicked the response. The selective 5-HT3 antagonist, ICS 205-930, blocked this response, but ketanserin and methiothepin did not affect it. The 5-HT-induced increase in Rin was blocked by 5-HT2 antagonists (ketanserin, methiothepin and spiperone); mimicked by alpha-methyl 5-HT, but not affected by 2-methyl 5-HT. The selective 5-HT3 antagonist, ICS 205-930, did not antagonize this response. The action of NE but not 5-HT was blocked by the selective alpha 1 antagonist, prazosin. These data indicate that the 5-HT induced depolarization with decreased Rin is mediated by 5-HT3 receptors and the depolarization with increased Rin is mediated by 5-HT2 receptors. Furthermore, these two receptors can occur on the same cell.
Todorović
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S
Department of Pharmacology, University of Illinois, College of Medicine, Chicago 60612.
Anderson
E G
EG
D000818:Animals; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*
D011985:Receptors, Serotonin; D012701:Serotonin; D009638:Norepinephrine