Lack of an interaction between orexinergic and opioid/nociceptinergic systems in rat cerebrocortical slices.
We have recently reported that orexins (OXs) selectively evoke norepinephrine release from rat cerebrocortical slices. In the present study, we have examined orexin-opioid interactions in OXA (100 nM) and K(+) (40 mM)-evoked norepinephrine release. OXA-evoked norepinephrine release was reversed approximately 90% by SB-334867 (OX(1)-receptor antagonist) (10 microM) but not naloxone (10 microM). [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE) (DOP-agonist) and nociceptin/orphanin-FQ (N/OFQ) also failed to affect OXA-evoked release. [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) (MOP-agonist) and spiradoline (KOP-agonist) significantly reduced OXA-evoked release with the concentration producing 50% of the maximal inhibition (EC(50)) [maximal inhibition (E(max))] of 3.2 microM [41.8%] and 4.3 microM [54.9%] respectively. The effects of DAMGO and spiradoline were naloxone (10 microM)-insensitive. In contrast, naloxone significantly antagonized the inhibitory effects of DAMGO and spiradoline on K(+)-evoked release. We conclude that opioid receptors (DOP and KOP) are involved in K(+) but not OXA-evoked release. Moreover, we have failed to demonstrate an interaction between orexinergic and opioid/N/OFQ-ergic systems in this system.
Hirota
Kazuyoshi
K
Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki 036-8563, Japan. masuila@cc.hirosaki-u.ac.jp
Kushikata
Tetsuya
T
Kudo
Mihoko
M
Ohkawa
Hirobumi
H
Kudo
Tsuyoshi
T
Lambert
David G
DG
Smart
Darren
D
Matsuki
Akitomo
A
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology* / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009479:Neuropeptides / Q000494:pharmacology* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D018847:Opioid Peptides / Q000494:pharmacology* / Q000502:physiology; D000068797:Orexins; D051381:Rats; D017208:Rats, Wistar; D000097629:Nociceptin
D000701:Analgesics, Opioid; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009292:Narcotic Antagonists; D009479:Neuropeptides; D009638:Norepinephrine; D018847:Opioid Peptides; D000068797:Orexins; D000097629:Nociceptin