The stereoselectivity of the serotonin(1 A) (5-HT1 A) receptor compound 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT) on forskolin-stimulated adenylyl cyclase activity was investigated in membranes from human 5-HT pre-synaptic (raphe nuclei) and post-synaptic (hippocampus and prefrontal cortex) regions of autopsy brains. After sample incubation with agonists and antagonists, results showed that both the racemic mixture of 8-OH-DPAT or its (+) and (-) enantiomers behaved as full agonists in the tested brain regions. Enantiomer potency (EC50, nM) and efficacy (percentage of maximal inhibition, %) values were similar in all regions under investigation. However, some inter and intra-region variations in racemic 8-OH-DPAT potency and efficacy have been observed. In particular, the potency of racemic 8-OH-DPAT was higher in the prefrontal cortex and raphe nuclei than in the hippocampus, where it was in fact lower than either single enantiomers. Agonist effects were competitively reversed by 5-HT1 A antagonists, although once again a different profile was revealed in the hippocampus. The data underscores the lack of stereospecificity of 8-OH-DPAT-mediated inhibition of adenylyl cyclase activity in either pre- or post-synaptic human brain regions. Moreover; such results have significant implication. as they support the notion that human 5-HT1 (A) receptors might vary from one brain region to the other. (C) 2000 Elsevier Science Ltd. All rights reserved.

Lack of stereoselectivity of 8-hydroxy-2(di-N-propylamino)tetralin-mediated inhibition of forskolin-stimulated adenylyl cyclase activity in human pre- and post-synaptic brain regions

PALEGO, LIONELLA;GIANNACCINI, GINO;NACCARATO, ANTONIO GIUSEPPE;LUCACCHINI, ANTONIO;MAZZONI, MARIA ROSA
2000

Abstract

The stereoselectivity of the serotonin(1 A) (5-HT1 A) receptor compound 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT) on forskolin-stimulated adenylyl cyclase activity was investigated in membranes from human 5-HT pre-synaptic (raphe nuclei) and post-synaptic (hippocampus and prefrontal cortex) regions of autopsy brains. After sample incubation with agonists and antagonists, results showed that both the racemic mixture of 8-OH-DPAT or its (+) and (-) enantiomers behaved as full agonists in the tested brain regions. Enantiomer potency (EC50, nM) and efficacy (percentage of maximal inhibition, %) values were similar in all regions under investigation. However, some inter and intra-region variations in racemic 8-OH-DPAT potency and efficacy have been observed. In particular, the potency of racemic 8-OH-DPAT was higher in the prefrontal cortex and raphe nuclei than in the hippocampus, where it was in fact lower than either single enantiomers. Agonist effects were competitively reversed by 5-HT1 A antagonists, although once again a different profile was revealed in the hippocampus. The data underscores the lack of stereospecificity of 8-OH-DPAT-mediated inhibition of adenylyl cyclase activity in either pre- or post-synaptic human brain regions. Moreover; such results have significant implication. as they support the notion that human 5-HT1 (A) receptors might vary from one brain region to the other. (C) 2000 Elsevier Science Ltd. All rights reserved.
Palego, Lionella; Giromella, A; Marazziti, D; Giannaccini, Gino; Borsini, F; Bigazzi, F; Naccarato, ANTONIO GIUSEPPE; Lucacchini, Antonio; Cassano, Gb; Mazzoni, MARIA ROSA
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/189221
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