Mu opioid receptor mRNA expression, binding, and functional coupling to G-proteins in human epileptic hippocampus.
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.
Epilepsy Clinic of Hospital General de Mexico, Mexico City, Mexico.
Manola
M
Cuellar-Herrera
Ana Luisa
AL
Velasco
Francisco
F
Velasco
Laura
L
Chavez
Sandra
S
Orozco-Suarez
Guliz
G
Armagan
Ezgi
E
Turunc
Engin
E
Bojnik
Ayfer
A
Yalcin
Sandor
S
Benyhe
Anna
A
Borsodi
Mario
M
Alonso-Vanegas
Luisa
L
Rocha
D000293:Adolescent; D000328:Adult; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
C404943:Oprm protein, mouse; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D019204:GTP-Binding Proteins