mu- and kappa-opioids inhibit K+ evoked glutamate release from rat cerebrocortical slices.
We have examined the effects of a range of opioid receptor subtype selective agonists on K+ evoked glutamate release from perfused rat cerebrocortical slices. Dual application (S1 and S2) of K+ (46 mM) evoked dual monophasic glutamate release profiles. When areas under the release curves were calculated an S2/S1 ratio for control slices of 1.07 +/- 0.08 (n = 75) was obtained, this was reduced by 80% with EGTA (0.1 mM) treatment confirming the presence of a Ca2+ regulated release process, Morphine produced a dose-dependent inhibition of the S2/S1 ratio. At 1 microM this amounted to 78 +/- 12% (mean +/- SEM; n = 6). (D-Ala2,MePhe4,gly(ol)5)enkephalin (DAMGO; 60 +/- 12%, n = 6 at 1 microM), and spiradoline (53 +/- 14% at 1 and 71 +/- 11% at 100 microM, both n = 6) also inhibited glutamate release in a cyprodime (10 microM) and norbinaltorphimine (10 microM) reversible manner. (D-Pen2.5) enkephalin (DPDPE; 1 microM) was ineffective. All agents tested did not affect basal glutamate release. Collectively these data implicate a role for mu and kappa opioids in the control of evoked glutamate release and their potential for neuroprotective therapy.
Nicol
B
B
University Department of Anaesthesia, Leicester Royal Infirmary, UK.
Rowbotham
D J
DJ
Lambert
D G
DG
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000700:Analgesics; D004745:Enkephalins; D009294:Narcotics; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D018698:Glutamic Acid; D009020:Morphine; D011188:Potassium