Potential differences in receptor-mediated G-protein activation in postmortem human hippocampal membranes prepared from healthy controls and suicide victims.

AIM

Postmortem brain studies offer enormous opportunities to study molecular mechanisms associated with suicide. In the present study, conventional [S]GTPγS binding assay and its version-up method ([S]GTPγS binding/immunoprecipitation assay) were applied to postmortem human hippocampal membranes prepared from suicide victims and control subjects.

METHODS

By using conventional [S]GTPγS binding assay, functional activations of G proteins coupled with multiple GPCRs (5-HT receptor, α-adrenoceptor, M/M mAChRs, adenosine A receptor, histamine H receptor, group II mGlu, GABA receptor, μ-opioid receptor, δ-opioid receptor, and NOP receptor) were detected by using 15 different agonists. Furthermore, 5-HT receptor- and M mAChR-mediated Gα activation and adenosine A receptor-mediated Gα activation were detectable by means of [S]GTPγS binding/immunoprecipitation assay.

RESULTS

No significant differences in pharmacological parameters of all concentration-response curves investigated were found between suicide victims and control subjects. Significant correlations were obtained for the maximal percent increases between some distinct signaling pathways.

CONCLUSION

Although only preliminary and auxiliary results were obtained as to the potential differences between suicide victims and control subjects because of the limited number of subjects as well as unmatched age and postmortem delay, adenosine A receptor-mediated Gα activation and 5-HT receptor-mediated Gα activation appear worth focusing on in the future investigations. This study also indicates the possibility that some distinct signaling pathways are interrelated with each other, for example, functional activations of G proteins coupled to M/M mAChR and 5-HT receptor, NOP receptor, and GABA receptor, and NOP receptor and δ-opioid receptor.