Changes in functional coupling of 5-HT 1A receptor to the G-protein in neocortex temporal tissues of patients with temporal lobe epilepsy

摘要

Background The 5-hydroxytryptamine-1A receptors are known to be involved in the inhibition of seizures in epilepsy. Objective The main aim of the present study is to determine the functional coupling to G-protein of the 5-HT 1A receptor through 8-OH-DPAT-stimulated [ 35 S]GTPγS binding assay in lateral temporal neocortex tissue of patients with mesial temporal lobe epilepsy (mTLE) and correlate it with clinical data. Material and methods The activation of the G protein complex was determined by [ 35 S]GTPγS binding assay. The temporal neocortex tissue was obtained from 5 patients with mTLE during epilepsy surgery and from 5 subjects (autopsies) who died due to an accident and without history of neurological disease. Results We found that values of maximal stimulation ( E max ) of [ 35 S]GTPγS binding significant decreased in the mTLE group (30.8%, p <.05) when compared to the autopsy samples (65.9%). The values of potency (pEC 50 ) were similar in both groups. However, we found no significant differences between the E max and age of patient, age of seizure onset, duration of epilepsy and frequency of seizures. Also, the pEC 50 values revealed no significant correlations with the clinical data. Conclusions Our data provide evidence that the lateral temporal neocortex of patients with pharmacoresistant mTLE presents alterations in the functional coupling to G-protein of the 5-HT 1A receptor. Such a change could be involved in hyperexcitability in the neocortex of patients with mTLE.