101. 5-HT1D as well as 5-HT1A autoreceptors modulate 5-HT release in the guinea-pig dorsal raphé nucleus
- Author
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S.J. Starkey and M. Skingle
- Subjects
Agonist ,Male ,Serotonin ,medicine.drug_class ,Guinea Pigs ,Pharmacology ,In Vitro Techniques ,Piperazines ,Cellular and Molecular Neuroscience ,Dorsal raphe nucleus ,medicine ,Animals ,Receptor ,GR-127935 ,Electrodes ,5-HT receptor ,8-Hydroxy-2-(di-n-propylamino)tetralin ,Oxadiazoles ,Chemistry ,Sumatriptan ,Receptor antagonist ,Serotonin Receptor Agonists ,Electrophysiology ,Receptors, Serotonin ,Autoreceptor ,Raphe Nuclei ,Serotonin Antagonists ,5-HT1D receptor ,Neuroscience ,Selective Serotonin Reuptake Inhibitors - Abstract
5-Hydroxytryptamine (5-HT) release was measured by fast cyclic voltammetry in guinea-pig dorsal raphé nucleus slices. Release was reproducibly evoked by a single 0.1 msec pulse of electrical stimulation. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH DPAT) produced a concentration-related inhibition of the stimulated 5-HT release, with 50% inhibition at 47 nM. This inhibition was competitively antagonized by N-tert-butyl 3-4-(2-methoxypheny)piperazin-1-yl-2- phenylpropanamide dihydrochloride [(+/-)WAY 100135], a selective 5-HT1A receptor antagonist (pA2 = 7.9). The 5-HT1D receptor agonist sumatriptan also produced a concentration-related inhibition of 5-HT release, with 50% inhibition at 40 nM. The effect of sumatriptan on 5-HT release was antagonized by the 5-HT1D receptor antagonist 2'-methyl-4'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxyli c acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide (GR127935) (pA2 = 8.7). Both (+/-)WAY 100135 and GR127935 increased the 5-HT release evoked by a train of 5 pulses at 1 Hz, suggesting that they were antagonizing the feedback of endogenously released 5-HT onto its autoreceptors. These findings demonstrate for the first time the presence of functional 5-HT1D as well as 5-HT1A autoreceptors in the guinea-pig dorsal raphé nucleus.
- Published
- 1994