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Dupuis, D.S. et al.

Autoradiographic studies of 5-HT1A-receptor-stimulated [35S]GTPgammaS-binding responses in the human and monkey brain.

G-protein activation mediated by serotonin 5-HT1A receptors in human and monkey brain was investigated by using quantitative autoradiography of agonist-stimulated [35S]GTPgammaS binding to whole-hemisphere brain sections. [35S]GTPgammaS binding was stimulated by the mixed 5-HT1A/1B/1D agonist L 694247 (10 microm) in human brain regions enriched in 5-HT1A binding sites [e.g. hippocampus (132-137%), superficial layers of the neocortex (37-61%), and cingulate and entorhinal cortex (34 and 32%, respectively)]. L 694247 caused virtually no stimulation in regions with 5-HT1B/1D receptors, such as substantia nigra, caudate nucleus and putamen. Similar results were obtained with monkey brain sections. The L 694247-mediated [35S]GTPgammaS-binding responses in human and monkey brain sections were antagonized by the selective, silent 5-HT1A antagonist WAY 100635 (10 microm). The 5-HT1B inverse agonist SB 224289 (10 microm) did not affect the [35S]GTPgammaS-binding response of L 694247. The distribution pattern of the [35S]GTPgammaS-binding response and the antagonist profile suggest the L 694247-induced response in human and monkey brain is mediated by 5-HT1A receptors. A weak stimulation of [35S]GTPgammaS binding was also observed in human hippocampus with either 10 microm 8-OH-DPAT (25 +/- 4%) or naratriptan (42 +/- 2%) compared with that obtained with L 694247. In conclusion, G-protein activation by 5-HT1A receptors can be measured in human and monkey brain sections. L 694247 appears to possess higher efficacy at 5-HT1A receptors compared with 8-OH-DPAT and naratriptan.[1]

References

Autoradiographic studies of 5-HT1A-receptor-stimulated [35S]GTPgammaS-binding responses in the human and monkey brain. Dupuis, D.S., Pauwels, P.J., Radu, D., Hall, H. Eur. J. Neurosci. (1999) [Pubmed]

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