Characterization of the 5‐Hydroxytryptamine Receptor Modulating the Release of 5‐[³H]Hydroxytryptamine in Slices of the Human Neocortex

Abstract

In the rat brain, the presynaptic 5-hydroxytryptamine (5-HT) autoreceptors located on 5-HT terminals correspond to the 5-HT1B subtype. The presence of a 5-HT receptor probably located on 5-HT nerve endings and modulating transmitter release in the human neocortex has been reported, but its detailed pharmacological characterization is not yet available. On the other hand, receptor binding and autoradiographic results indicate that the 5-HT1B receptor subtype is not present in the human brain. We, therefore, studied the modulation of the electrically evoked release of [3H]5-HT by various 5-HT receptor agonists and antagonists in preloaded slices of human neocortex obtained from 18 patients undergoing neurosurgery. The nonselective 5-HT1A/1B/1D receptor agonist 5-carboxamidotryptamine produced a potent inhibition (70% at 0.03 microM) of the electrically evoked release of [3H]5-HT which was blocked by 5-HT receptor antagonists with the following relative order of potency: methiothepin greater than metergoline = methysergide greater than propranolol. The selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin at 0.1 microM did not modify the electrically evoked release of [3H]5-HT. The 5-HT1A/1B receptor agonist RU 24969 was 10 times more potent at inhibiting [3H]5-HT overflow in the rat frontal cortex than in the human neocortex. The potent 5-HT1B receptor antagonist cyanopinodolol did not modify the 5-carboxamidotryptamine-induced inhibition of the electrically evoked release of [3H]5-HT in slices of the human neocortex, but produced by itself a small inhibition of [3H]5-HT overflow.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic Evidence for Desensitization of α2-Adrenoceptors on Serotonin Terminals Following Long-Term Treatment with Drugs Increasing Norepinephrine Synaptic Concentration

“…Using an in vivo elec trophysiologic paradigm, it was recently shown that these u2-adrenergic heteroreceptors in the rat hip pocampus are tonically activated by endogenous NE (Mongeau et al 1993), as is the case in the human brain (Galzin et al 1992;Feuerstein et al 1993). Small doses (2 �g/kg and 10 �g/kg IV) of the u2-adrenergic agonist clonidine enhance 5-HT neurotransmission, an effect that is abolished by a 6-hydroxydopamine (6-0HDA) pretreatment and blocked by the u2-adrenergic an tagonist yohimbine (0.1 mg/kg IV).…”

[3H]-Serotonin Release from Bovine Iris-ciliary Body: Pharmacology of Prejunctional Serotonin (5-HT7) Autoreceptors

“…When stimulated via electrical means or by depolarization with agents such as potassium ions, 5-HT can be released from nerves, in vitro (Monroe and Smith, 1985;Galzin et al, 1992;Moret and Briley, 1997). In the eye, serotonin-containing nerve ®bers have been localized in the iris-ciliary bodies and corneas of guinea pigs, rats and rabbits (Uusitalo et al, 1982;Tobin et al, 1988).…”

Serotonin decreases generation of dopaminergic neurons from mesencephalic precursors via serotonin type 7 and type 4 receptors

“…The results of several recent studies suggest that in very early stages of development 5-HT 1B/1D and 5-HT 1A receptors may act as 5-HT autoreceptors, so that 5-HT synthesis, storage, and uptake may be down-regulated by 5-HT itself (Héry et al, 1999;Mouillet-Richardet al, 2000;Roberts et al, 2001;Rumajogee et al, 2004). It has been suggested that 5-HT 1B autoreceptors diminish 5-HT release from axon terminals and varicosities (Galzin et al, 1992), while 5-HT 1A autoreceptors inhibit firing of serotonergic neurons (Sprouse and Aghanian, 1987;Héry et al, 1999;. Furthermore, it has recently been observed that the lack of 5-HT 1B or 5-HT 1A receptors is associated with a significant increase in the number of serotonergic neurons in primary cultures from embryonic raphe (Rumajogee et al, 2004).…”