5-HT1D as well as 5-HT1A autoreceptors modulate 5-HT release in the guinea-pig dorsal raphé nucleus.
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.
Starkey
S J
SJ
Department of Pharmacology, Glaxo Research and Development Ltd., Ware, Herts, U.K.
Skingle
M
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D004566:Electrodes; D004594:Electrophysiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010069:Oxadiazoles; D010879:Piperazines; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D018170:Sumatriptan; C081293:WAY 100135; C090701:GR 127935