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Mu opioid receptor mRNA expression, binding, and functional coupling to G-proteins in human epileptic hippocampus
Manola Cuellar-Herrera1, Ana Luisa Velasco, Francisco Velasco
1Epilepsy Clinic of Hospital General de Mexico, Mexico City, Mexico.
Abstract:
Mu opioid receptors (MOR) are known to be involved in seizure activity. The main goal of the present study was to characterize the MOR mRNA expression, binding, as well as G protein activation mediated by these receptors in epileptic hippocampus of patients with pharmacoresistant mesial temporal lobe epilepsy (TLE). In contrast with autopsy samples, hippocampus obtained from patients with mesial TLE demonstrated enhanced MOR mRNA expression (116%). Saturation binding experiments revealed significantly higher (60%) B(max) values for the mesial TLE group, whereas the K(d) values were not statistically different. Although mesial TLE group demonstrated high levels of basal binding for the G proteins (136%), DAMGO-stimulated [(35)S]GTPγS binding did not demonstrate significant alterations. In conclusion, our present data provide strong evidence that the epileptic hippocampus of patients with pharmacoresistant mesial TLE presents significant alterations in MOR. Such changes may represent adaptive mechanisms to compensate for other as yet unknown alterations.
Insights
This study found increased mu opioid receptor (MOR) mRNA and binding in the hippocampus of epilepsy patients. These changes in MOR may be an adaptive response to pharmacoresistant mesial temporal lobe epilepsy (TLE).
Area of Science:
- Neuroscience
- Epileptology
- Pharmacology
Background:
- Mu opioid receptors (MOR) play a role in seizure activity.
- Pharmacoresistant mesial temporal lobe epilepsy (TLE) presents challenges in treatment.
- Understanding receptor alterations in epilepsy is crucial for therapeutic development.
Purpose of the Study:
- To characterize MOR mRNA expression, binding, and G protein activation in the epileptic hippocampus of pharmacoresistant TLE patients.
- To compare these parameters between TLE patients and control (autopsy) samples.
- To investigate potential adaptive mechanisms in the epileptic brain.
Main Methods:
- Quantitative analysis of MOR mRNA expression in hippocampal tissue.
- Saturation binding experiments to determine receptor density (Bmax) and affinity (Kd).
- G protein activation assays using radioligand binding ([(35)S]GTPγS) with and without MOR agonist stimulation (DAMGO).
Main Results:
- Hippocampus from TLE patients showed significantly enhanced MOR mRNA expression (116%) compared to autopsy samples.
- Saturation binding revealed a 60% higher Bmax for MOR in the TLE group, with no significant change in Kd.
- Basal G protein binding was elevated in the TLE group, but DAMGO-stimulated binding showed no significant alterations.
Conclusions:
- The epileptic hippocampus in pharmacoresistant TLE exhibits significant alterations in mu opioid receptors.
- Increased MOR mRNA and binding capacity suggest an adaptive response within the epileptic brain.
- These MOR changes might compensate for other unidentified pathological alterations in TLE.
