Actions of the prototypical 5-HT1A receptor agonist 8-OH-DPAT at human α2-adrenoceptors: (+)8-OH-DPAT, but not (−)8-OH-DPAT is an α2B subtype preferential agonist

Heusler, Peter; Rauly‐Lestienne, Isabelle; Tourette, Amélie; Tardif, Stéphanie; Ailhaud, Marie-Christine; Croville, Guillaume; Cussac, Didier

doi:10.1016/j.ejphar.2010.04.034

Cited by 5 publications

(5 citation statements)

References 42 publications

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“…Moreover, although studies using native tissue have strong biological significance, membranes prepared from rat cerebral cortex contain other receptors that can be targeted by [ 3 H]-8-OH-DPAT (i.e. serotonin 5-HT 7 receptors and α-2 adrenergic receptors) [14, 15], which might create an additional level of complexity in the interactions of Zn at 5-HT 1A Rs. As allosteric modulation is strongly probe-dependent [16], evaluation of the effects of Zn on agonist binding is of primary importance to its action observed in vivo.…”

Section: Introductionmentioning

confidence: 99%

Concentration-Dependent Dual Mode of Zn Action at Serotonin 5-HT1A Receptors: In Vitro and In Vivo Studies

et al. 2015

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Recent data has indicated that Zn can modulate serotonergic function through the 5-HT1A receptor (5-HT1AR); however, the exact mechanisms are unknown. In the present studies, radioligand binding assays and behavioural approaches were used to characterize the pharmacological profile of Zn at 5-HT1ARs in more detail. The influence of Zn on agonist binding to 5-HT1ARs stably expressed in HEK293 cells was investigated by in vitro radioligand binding methods using the agonist [3H]-8-OH-DPAT. The in vivo effects of Zn were compared with those of 8-OH-DPAT in hypothermia, lower lip retraction (LLR), 5-HT behavioural syndrome and the forced swim (FST) tests. In the in vitro studies, biphasic effects, which involved allosteric potentiation of agonist binding at sub-micromolar Zn concentrations and inhibition at sub-millimolar Zn concentrations, were found. The in vivo studies showed that Zn did not induce LLR or elements of 5-HT behavioural syndrome but blocked such effects induced by 8-OH-DPAT. Zn decreased body temperature in rats and mice; however, Zn failed to induce hypothermia in the 5-HT1A autoreceptor knockout mice. In the FST, Zn potentiated the effect of 8-OH-DPAT. However, in the FST performed with the 5-HT1A autoreceptor knockout mice, the anti-immobility effect of Zn was partially blocked. Both the binding and behavioural studies suggest a concentration-dependent dual mechanism of Zn action at 5-HT1ARs, with potentiation at low dose and inhibition at high dose. Moreover, the in vivo studies indicate that Zn can modulate both presynaptic and postsynaptic 5-HT1ARs; however, Zn’s effects at presynaptic receptors seem to be more potent.

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Section: Introductionmentioning

confidence: 99%

Concentration-Dependent Dual Mode of Zn Action at Serotonin 5-HT1A Receptors: In Vitro and In Vivo Studies

et al. 2015

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“…The discovery of (±)8-OH-DPAT as a 5-HT 1A R agonist revolutionized 5-HT 1A R research (Duncan et al, 1998; Simpson et al, 1996; Trillat et al, 1998). Although additional radioligands have been reported over the years, [ 3 H]8-OH DPAT remains the most widely used agonist radioligand for in vitro quantification of 5-HT 1A R sites, despite its moderate affinity for some non-5-HT 1A targets including 5-HT 7 R, 5-HT 1B/D R, α2-adrenergic receptor (α2-AR), D 2 -like receptors and the serotonin transporter (Heusler et al, 2010; Nenonene et al, 1994; Sprouse et al, 2004). As a result, [ 3 H]8-OH-DPAT binding in 5-HT 1A R knockout mice has detectable binding to 5-HT 7 R and α 2- AR.…”

Section: Introductionmentioning

confidence: 99%

Autoradiographic evaluation of [3H]CUMI-101, a novel, selective 5-HT1AR ligand in human and baboon brain

et al. 2013

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[11C]CUMI-101 is the first selective serotonin receptor (5-HT1AR) partial agonist radiotracer for positron emission tomography (PET) tested in vivo in nonhuman primates and humans. We evaluated specific binding of [3H]CUMI-101 by quantitative autoradiography studies in postmortem baboon and human brain sections using the 5- HT1AR antagonist WAY100635 as a displacer. The regional and laminar distributions of [3H]CUMI-101 binding in baboon and human brain sections matched the known distribution of [3H]8-OH-DPAT and [3H]WAY100635. Prazosin did not measurably displace [3H]CUMI-101 binding in baboon or human brain sections, thereby ruling out [3H]CUMI-101 binding to α1-adrenergic receptors. This study demonstrates that [11C]CUMI-101 is a selective 5-HT1AR ligand for in vivo and in vitro studies in baboon and human brain.

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“…By comparison, as mentioned above, 8-OH-DPAT interacts with non-5-HT 1A receptors such as the 5-HT transporter Koek, 1996, 2000) and alpha-adrenoceptors (Heusler et al, 2010), while sarizotan (Bartoszyk et al, 2004) and tandospirone (Hamik et al, 1990) antagonise dopamine receptors, which might account for their narrow therapeutic window. Further studies, including higher doses of F15599, are required, to define the upper extent of its therapeutic window and fully characterise its potential as a new anti-dyskinetic agent in PD.…”

Section: Discussionmentioning

confidence: 97%

The highly-selective 5-HT1A agonist F15599 reduces l-DOPA-induced dyskinesia without compromising anti-parkinsonian benefits in the MPTP-lesioned macaque

et al. 2015

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Actions of the prototypical 5-HT1A receptor agonist 8-OH-DPAT at human α2-adrenoceptors: (+)8-OH-DPAT, but not (−)8-OH-DPAT is an α2B subtype preferential agonist

Cited by 5 publications

References 42 publications

Concentration-Dependent Dual Mode of Zn Action at Serotonin 5-HT1A Receptors: In Vitro and In Vivo Studies

Concentration-Dependent Dual Mode of Zn Action at Serotonin 5-HT1A Receptors: In Vitro and In Vivo Studies

Autoradiographic evaluation of [3H]CUMI-101, a novel, selective 5-HT1AR ligand in human and baboon brain

The highly-selective 5-HT1A agonist F15599 reduces l-DOPA-induced dyskinesia without compromising anti-parkinsonian benefits in the MPTP-lesioned macaque

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