Nociceptin/orphanin FQ inhibits glutamate release from rat cerebellar and brain stem slices.
We have previously demonstrated that nociceptin/orphanin FQ (N/OFQ), inhibits K(+) depolarisation-evoked glutamate release from rat cerebrocortical slices. In this study we have examined the effects of N/OFQ on glutamate release from rat cerebellar and brain stem slices as there are regional differences in nociceptin/orphanin FQ receptor (NOP) expression. Slices were depolarised with two pulses of 46 mM K(+) (S(1) and S(2)) with N/OFQ added after S(1). Glutamate (non-radioactive) was measured using a fluorescence-based assay. N/OFQ effects were assessed by measuring area under S(1) and S(2) release curves and calculation of S(2)/S(1) ratios. In cerebellar slices K(+) evoked S(2)/S(1) ratio was 1.17+/-0.10 (n=28). This was reduced in a concentration dependent (EC(50) 22 nM; E(max) 46%) and naloxone (10 microM) insensitive manner by N/OFQ. In the brain stem K(+) evoked glutamate release was considerably reduced compared to cerebellum. In several preparations K(+) failed to evoke a significant release. In those that did K(+) evoked S(2)/S(1) ratio was 1.03+/-0.07 (n=13). A total of 100 nM N/OFQ reduced this by 38+/-12% and this response was naloxone insensitive. Due to this small response and its variability we could not construct a full concentration response curve. In conclusion we have demonstrated a functional NOP in rat cerebellum and brain stem that inhibits the release of glutamate.
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University Department of Anaesthesia, Critical Care and Pain Management, Leicester Royal Infirmary, Leicester LE1 5WW, UK.
Rowbotham
D J
DJ
Lambert
D G
DG
D000818:Animals; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D018690:Excitatory Amino Acid Agonists; D018698:Glutamic Acid; D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011188:Potassium; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat