Serotonin-induced reduction of the calcium-dependent plateau in frog dorsal root ganglion cells is blocked by serotonergic agents acting at 5-hydroxytryptamine1A sites.
Intracellular recordings from the dorsal root ganglion cells of adult frogs in the presence of tetraethylammonium display action potentials with a prominent calcium-dependent plateau. These action potentials can be altered by serotonergic agents in one of two ways. The superfusion of 5-HT (0.1-1 microM) usually produces a dose-dependent reduction of the action potential duration, whereas 8-hydroxy dipropylaminotetralin (8-OH-DPAT) (10-50 microM) produces a dose-dependent increase in duration. A series of 5-HT antagonists were tested for their ability to block either the 5-HT or the 8-OH-DPAT effect. The antagonists were chosen for their reported selectivity in distinguishing receptors of the 5-HT1A, 5-HT2 and 5-HT3 subtypes. The antagonists' action on 5-HT narrowing [blockade by methiothepin, spiperone and spiroxitrine, but not by ketanserin or 3-tropyl-indole-3-carboxylate (ICS 205-930)] suggests that this response is mediated by 5-HT1A receptors. The widening effect produced by 8-OH-DPAT (a putative 5-HT1A agonist) was not blocked by any antagonist tested. At lower concentrations (0.1-2.5 microM) 8-OH-DPAT exhibited no agonist actions, but antagonized the 5-HT-induced narrowing. These results suggest the 5-HT receptors mediating 5-HT action potential narrowing in these cells are of the 5-HT1A subtype, but that they differ from the 5-HT1A receptors described in other tissues in which 8-OH-DPAT is an agonist or a partial agonist.
Marszalec
W
W
Department of Pharmacology, University of Illinois Medical College, Chicago.
Scroggs
R S
RS
Anderson
E G
EG
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004146:Dioxanes / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D008719:Methiothepin / Q000494:pharmacology; D011892:Rana catesbeiana; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D004146:Dioxanes; D011985:Receptors, Serotonin; D013141:Spiro Compounds; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D013134:Spiperone; D008719:Methiothepin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C018387:spiroxatrine; D002118:Calcium