Serotonin agonists inhibit synaptic potentials in the rat locus ceruleus in vitro via 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) receptors

D. H. Bobker, John Williams

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Abstract

Intracellular recordings were made from rat locus ceruleus neurons in the slice preparation in vitro. Depolarizing synaptic potentials (DSP)2 elicited by electrical stimulation were typically 10 to 15 mV in amplitude and 200 msec in duration. Superfusion with 5-hydroxytryptamine (5-HT, serotonin) or the 5-HT1 receptor agonist 5-carboxamidotryptamine (5-CT), produced an inhibition of the DSP. The maximal inhibition was 55 ± 2% (mean ± S.E.M.). The EC50 for 5-CT was 60 nM, whereas for 5-HT it was 12 μM. Cocaine (10 μM) shifted the 5-HT concentration-response curve to the left and the EC50 to 320 nM. 8-Hydroxy-2-(di-n-propylamino)tetralin, a selective 5-HT(1A) receptor ligand, also inhibited the DSP, but only produced about 65% of the maximal 5-CT or 5-HT response (EC50 = 50 nM). A relatively selective 5-HT(1B) ligand (65-fold 5-HT(1B) > 5-HT(1A)), 1-(m-trifluoromethylphenyl)-piperazine, acted as a full agonist (EC50 = 110 nM). None of these compounds had any effects on the membrane properties of the cell at the doses tested. The response to 8-hydroxy-2-(di-n-propylamino) tetralin was antagonized by pretreatment with the 5-HT(1A) antagonist spiperone (1 μM). The estimated K(D) for spiperone was 16 nM. At this same concentration, however, there was no effect on the 5-CT-induced inhibition. The antagonist 4-(3-ter-butyl-amino-2-hydroxy-propoxyl)-indol-2-carbonic acid isopropyl ester (LM 21-009, 100 nM) was found to be a partial agonist producing a 26 ± 4% inhibition of the DSP. In addition, LM 21-009 shifted the 5-CT concentration-response curve right in a nonparallel manner. The estimated K(D) was 4.2 nM. This pharmacologic profile suggests that the presynaptic inhibition of the DSP is mediated by both 5-HT(1A) and 5-HT(1B) receptors.

Original languageEnglish (US)
Pages (from-to)37-43
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume250
Issue number1
StatePublished - 1989

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Receptor, Serotonin, 5-HT1B
Serotonin Receptor Agonists
Synaptic Potentials
Locus Coeruleus
Serotonin
Spiperone
8-Hydroxy-2-(di-n-propylamino)tetralin
Carbonic Acid
Ligands
Serotonin 5-HT1 Receptor Agonists
In Vitro Techniques
Serotonin Antagonists
Receptor, Serotonin, 5-HT1A
Cocaine
Electric Stimulation
Esters
Cell Membrane
5-carboxamidotryptamine
Neurons

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{e658b863e0004cad8d9d4140df5e9cbc,
title = "Serotonin agonists inhibit synaptic potentials in the rat locus ceruleus in vitro via 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) receptors",
abstract = "Intracellular recordings were made from rat locus ceruleus neurons in the slice preparation in vitro. Depolarizing synaptic potentials (DSP)2 elicited by electrical stimulation were typically 10 to 15 mV in amplitude and 200 msec in duration. Superfusion with 5-hydroxytryptamine (5-HT, serotonin) or the 5-HT1 receptor agonist 5-carboxamidotryptamine (5-CT), produced an inhibition of the DSP. The maximal inhibition was 55 ± 2{\%} (mean ± S.E.M.). The EC50 for 5-CT was 60 nM, whereas for 5-HT it was 12 μM. Cocaine (10 μM) shifted the 5-HT concentration-response curve to the left and the EC50 to 320 nM. 8-Hydroxy-2-(di-n-propylamino)tetralin, a selective 5-HT(1A) receptor ligand, also inhibited the DSP, but only produced about 65{\%} of the maximal 5-CT or 5-HT response (EC50 = 50 nM). A relatively selective 5-HT(1B) ligand (65-fold 5-HT(1B) > 5-HT(1A)), 1-(m-trifluoromethylphenyl)-piperazine, acted as a full agonist (EC50 = 110 nM). None of these compounds had any effects on the membrane properties of the cell at the doses tested. The response to 8-hydroxy-2-(di-n-propylamino) tetralin was antagonized by pretreatment with the 5-HT(1A) antagonist spiperone (1 μM). The estimated K(D) for spiperone was 16 nM. At this same concentration, however, there was no effect on the 5-CT-induced inhibition. The antagonist 4-(3-ter-butyl-amino-2-hydroxy-propoxyl)-indol-2-carbonic acid isopropyl ester (LM 21-009, 100 nM) was found to be a partial agonist producing a 26 ± 4{\%} inhibition of the DSP. In addition, LM 21-009 shifted the 5-CT concentration-response curve right in a nonparallel manner. The estimated K(D) was 4.2 nM. This pharmacologic profile suggests that the presynaptic inhibition of the DSP is mediated by both 5-HT(1A) and 5-HT(1B) receptors.",
author = "Bobker, {D. H.} and John Williams",
year = "1989",
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volume = "250",
pages = "37--43",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
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T1 - Serotonin agonists inhibit synaptic potentials in the rat locus ceruleus in vitro via 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) receptors

AU - Bobker, D. H.

AU - Williams, John

PY - 1989

Y1 - 1989

N2 - Intracellular recordings were made from rat locus ceruleus neurons in the slice preparation in vitro. Depolarizing synaptic potentials (DSP)2 elicited by electrical stimulation were typically 10 to 15 mV in amplitude and 200 msec in duration. Superfusion with 5-hydroxytryptamine (5-HT, serotonin) or the 5-HT1 receptor agonist 5-carboxamidotryptamine (5-CT), produced an inhibition of the DSP. The maximal inhibition was 55 ± 2% (mean ± S.E.M.). The EC50 for 5-CT was 60 nM, whereas for 5-HT it was 12 μM. Cocaine (10 μM) shifted the 5-HT concentration-response curve to the left and the EC50 to 320 nM. 8-Hydroxy-2-(di-n-propylamino)tetralin, a selective 5-HT(1A) receptor ligand, also inhibited the DSP, but only produced about 65% of the maximal 5-CT or 5-HT response (EC50 = 50 nM). A relatively selective 5-HT(1B) ligand (65-fold 5-HT(1B) > 5-HT(1A)), 1-(m-trifluoromethylphenyl)-piperazine, acted as a full agonist (EC50 = 110 nM). None of these compounds had any effects on the membrane properties of the cell at the doses tested. The response to 8-hydroxy-2-(di-n-propylamino) tetralin was antagonized by pretreatment with the 5-HT(1A) antagonist spiperone (1 μM). The estimated K(D) for spiperone was 16 nM. At this same concentration, however, there was no effect on the 5-CT-induced inhibition. The antagonist 4-(3-ter-butyl-amino-2-hydroxy-propoxyl)-indol-2-carbonic acid isopropyl ester (LM 21-009, 100 nM) was found to be a partial agonist producing a 26 ± 4% inhibition of the DSP. In addition, LM 21-009 shifted the 5-CT concentration-response curve right in a nonparallel manner. The estimated K(D) was 4.2 nM. This pharmacologic profile suggests that the presynaptic inhibition of the DSP is mediated by both 5-HT(1A) and 5-HT(1B) receptors.

AB - Intracellular recordings were made from rat locus ceruleus neurons in the slice preparation in vitro. Depolarizing synaptic potentials (DSP)2 elicited by electrical stimulation were typically 10 to 15 mV in amplitude and 200 msec in duration. Superfusion with 5-hydroxytryptamine (5-HT, serotonin) or the 5-HT1 receptor agonist 5-carboxamidotryptamine (5-CT), produced an inhibition of the DSP. The maximal inhibition was 55 ± 2% (mean ± S.E.M.). The EC50 for 5-CT was 60 nM, whereas for 5-HT it was 12 μM. Cocaine (10 μM) shifted the 5-HT concentration-response curve to the left and the EC50 to 320 nM. 8-Hydroxy-2-(di-n-propylamino)tetralin, a selective 5-HT(1A) receptor ligand, also inhibited the DSP, but only produced about 65% of the maximal 5-CT or 5-HT response (EC50 = 50 nM). A relatively selective 5-HT(1B) ligand (65-fold 5-HT(1B) > 5-HT(1A)), 1-(m-trifluoromethylphenyl)-piperazine, acted as a full agonist (EC50 = 110 nM). None of these compounds had any effects on the membrane properties of the cell at the doses tested. The response to 8-hydroxy-2-(di-n-propylamino) tetralin was antagonized by pretreatment with the 5-HT(1A) antagonist spiperone (1 μM). The estimated K(D) for spiperone was 16 nM. At this same concentration, however, there was no effect on the 5-CT-induced inhibition. The antagonist 4-(3-ter-butyl-amino-2-hydroxy-propoxyl)-indol-2-carbonic acid isopropyl ester (LM 21-009, 100 nM) was found to be a partial agonist producing a 26 ± 4% inhibition of the DSP. In addition, LM 21-009 shifted the 5-CT concentration-response curve right in a nonparallel manner. The estimated K(D) was 4.2 nM. This pharmacologic profile suggests that the presynaptic inhibition of the DSP is mediated by both 5-HT(1A) and 5-HT(1B) receptors.

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