Diverse actions of 5-hydroxytryptamine on frog spinal dorsal horn neurons in vitro.
The effects of 5-hydroxytryptamine on the membrane potential and input resistance of 86 dorsal horn neurons were studied using intracellular recordings in isolated, hemisected spinal cords of adult frogs (Rana pipiens). Bath application of serotonin (5-100 microM) caused membrane depolarizations in 58 (67%) neurons, hyperpolarizations in 12 (14%) cells, biphasic responses in nine (11%) neurons, and no detectable change in seven (8%) cells. In some neurons depolarized by serotonin, the amine's responses could be mimicked by the selective 5-HT2 agonist (+/-)-1(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride and the 5-HT1C/2 agonist alpha-methyl-5-hydroxytryptamine, and blocked by the 5-HT1C/2 antagonists ketanserin and mianserin. In other neurons depolarized by serotonin, the 5-HT3 agonist 2-methyl-5-hydroxytryptamine mimicked, and the 5-HT3 antagonist, 3-tropanyl-3,5-dichlorobenzoate, blocked the serotonin-induced responses. Depolarizing responses due to activation of 5-HT1C/2 receptors were generally accompanied by increases in the membrane input resistance, whereas depolarizations mediated by 5-HT3 receptors were associated with a decreased membrane input resistance. Superfusion with tetrodotoxin or low-Ca2+/high-Mg(2+)-containing media abolished about half of the depolarizing responses. Hyperpolarizations caused by serotonin were associated with a decrease in membrane input resistance, and might have been due to activation of a potassium conductance. These responses persisted in bathing solutions containing tetrodotoxin or low-Ca2+/high-Mg2+. The 5-HT1A agonist 8-hydroxy-2-(di-N-propylamine)tetralin hydrobromide mimicked, whereas the 5-HT1A antagonist spiroxatrine blocked, these hyperpolarizing responses. Other antagonists selective for 5-HT1C/2 or 5-HT3 receptors were without effect. Serotonin-produced biphasic responses consisted of either an initial depolarization followed by a hyperpolarization or the reverse. The selective 5-HT2 agonist (+/-)-1(2,5-dimethyoxy-4-iodophenyl)-2-aminopropane hydrochloride could only mimic the depolarizations, whereas the 5-HT1A agonist 8-hydroxy-2-(di-N-propylamine)tetralin hydrobromide produced only the hyperpolarizations. Spiroxatrine, a 5-HT1A antagonist, blocked only the hyperpolarizations without affecting the depolarizations, and methysergide, a non-specific 5-HT receptor antagonist, depressed both the depolarizations and hyperpolarizations. Serotonin also appeared to affect spinal dorsal horn neurons indirectly because it produced excitatory postsynaptic potentials, inhibitory postsynaptic potentials, and a mixture of both.(ABSTRACT TRUNCATED AT 400 WORDS)
Tan
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Department of Comparative Biosciences, University of Wisconsin-Madison 53706.
Miletic
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008784:Methysergide / Q000494:pharmacology; D008803:Mianserin / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011894:Rana pipiens; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000502:physiology*; D013141:Spiro Compounds / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014326:Tropanes / Q000494:pharmacology
D000662:Amphetamines; D004146:Dioxanes; D012702:Serotonin Antagonists; D013141:Spiro Compounds; D014326:Tropanes; D008803:Mianserin; D012701:Serotonin; D013779:Tetrodotoxin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; C018387:spiroxatrine; C042253:bemesetron; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D008784:Methysergide