Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites

Abstract

In rat brain cortex slices preincubated with [3H]5-HT, the potencies of 17 5-HT receptor agonists to inhibit the electrically evoked 3H overflow and the affinities of 13 antagonists (including several beta-adrenoceptor blocking agents) to antagonize competitively the inhibitory effect of unlabelled 5-HT on evoked 3H overflow were determined. The affinities of the compounds for 5-HT1B and 5-HT2 binding sites in rat brain cortex membranes (labelled by [125I]cyanopindolol = [125I]-CYP in the presence of 30 mumol/l isoprenaline and [3H]ketanserin, respectively), for 5-HT1A binding sites in pig and rat brain cortex membranes (labelled by [3H]8-hydroxy-2-(di-n-propylamino)tetralin = [3H]8-OH-DPAT) and for 5-HT1C binding sites in pig choroid plexus membranes (labelled by [3H]mesulergine) were also determined. The affinities of the drugs for the various 5-HT recognition sites ranged over 4-5 log units (the functional experiments revealed the same range of differences between the drugs). There were no significant correlations between the affinities of the drugs at 5-HT1C and 5-HT2 binding sites and their potencies or affinities, determined for the 5-HT autoreceptors. In contrast, significant correlations were found between the potencies or affinities of the drugs for the autoreceptors and their affinities at 5-HT1A or 5-HT1B binding sites; the best correlations were obtained with the 5-HT1B binding site. Some of the drugs investigated were not included in the correlation since their agonistic or antagonistic effects on the autoreceptors were weak and pEC30 or apparent pA2 values could not be determined (less than 5.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Potentiation by (-)Pindolol of the Activation of Postsynaptic 5-HT1A Receptors Induced by Venlafaxine

“…(-)Pindolol bears significant affinity for the 5-HT 1B receptor (Hoyer et al 1985) which is known to negatively regulate the release of 5-HT in terminal areas of the rat brain (Engel et al 1986). Given that in functional assays (-)pindolol acts as an antagonist at the latter receptor (Schoeffter and Hoyer 1989), it is plausible that the latter property could account, at least in part, for the potentiating effect of (-)pindolol on the suppressant effect of venlafaxine on the firing activity of hippocampal neurons that was observed in the present study.…”

Transcriptional regulation of the 5-HT1Areceptor: implications for mental illness

“…In 5-HT 1A knockout animals, an elevated basal raphe firing may result from a chronic absence of 5-HT 1A receptors. By contrast, the 5-HT 1B subtype is the key autoreceptor on presynaptic 5-HT nerve terminals regulating 5-HT release [21,22]. Recently, targeting of the 5-HT 1A autoreceptor to soma and dendrites has been shown to be mediated by interaction of the receptor C-terminal tail with Yif1B [23,24].…”

Sex Differences in the Regulation of Serotonergic Transmission and Behavior in 5-HT Receptor Knockout Mice

“…The 5-HT 1B receptor functions presynaptically as an inhibitory autoreceptor located on terminals of 5-HT neurons (Engel et al, 1986). 5-HT 1B receptors also function postsynaptically as inhibitory heteroreceptors to control the release of other neurotransmitters (Boschert et al, 1994;Moret and Briley, 1997;Adell et al, 2001).…”

“…5-HT 1B receptors are located on terminals presynaptically and postsynaptically relative to 5-HT neurons. Presynaptic 5-HT 1B receptors are autoreceptors that regulate terminal release, whereas postsynaptic 5-HT 1B receptors are heteroreceptors located at nerve terminals that regulate the release of other neurotransmitters (Engel et al, 1986;Adell et al, 2001). The 5-HT 1B receptor has been localized to a variety of brain regions including the basal ganglia and hippocampus (Boschert et al, 1994).…”