Temporal lobe epilepsy causes selective changes in mu opioid and nociceptin receptor binding and functional coupling to G-proteins in human temporal neocortex.
There is no information concerning signal transduction mechanisms downstream of the opioid/nociceptin receptors in the human epileptic brain. The aim of this work was to evaluate the level of G-proteins activation mediated by DAMGO (a mu receptor selective peptide) and nociceptin, and the binding to mu and nociceptin (NOP) receptors and adenylyl cyclase (AC) in neocortex of patients with pharmacoresistant temporal lobe epilepsy. Patients with temporal lobe epilepsy associated with mesial sclerosis (MTLE) or secondary to tumor or vascular lesion showed enhanced [3H]DAMGO and [3H]forskolin binding, lower DAMGO-stimulated [35S]GTPgammaS binding and no significant changes in nociceptin-stimulated G-protein. [3H]Nociceptin binding was lower in patients with MTLE. Age of seizure onset correlated positively with [3H]DAMGO binding and DAMGO-stimulated [35S]GTPgammaS binding, whereas epilepsy duration correlated negatively with [3H]DAMGO and [3H]nociceptin binding, and positively with [3H]forskolin binding. In conclusion, our present data obtained from neocortex of epileptic patients provide strong evidence that a) temporal lobe epilepsy is associated with alterations in mu opioid and NOP receptor binding and signal transduction mechanisms downstream of these receptors, and b) clinical aspects may play an important role on these receptor changes.
Rocha
Luisa
L
Department of Pharmacobiology, Center of Research and Advanced Studies, Mexico City, Mexico. lrocha@cinvestav.mx
Orozco-Suarez
Sandra
S
Alonso-Vanegas
Mario
M
Villeda-Hernandez
Juana
J
Gaona
Andres
A
Páldy
Eszter
E
Benyhe
Sandor
S
Borsodi
Anna
A
D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D002491:Central Nervous System Agents / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism*; D018847:Opioid Peptides / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D013702:Temporal Lobe / Q000378:metabolism*; D014316:Tritium; D055815:Young Adult; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000262:Adenylyl Cyclases; D002491:Central Nervous System Agents; D005576:Colforsin; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019204:GTP-Binding Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D018847:Opioid Peptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D013462:Sulfur Radioisotopes; D014316:Tritium; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C485764:OPRM1 protein, human; C000722283:OPRL1 protein, human