Role of nociceptin/orphanin FQ and the pseudopeptide [Phe1Psi(CH2NH)Gly2]-nociceptin(1-13)-NH2 and their interaction with classic opioids in the modulation of thermonociception in the land snail Helix aspersa.
The role in nociception of nociceptin/orphanin FQ (N/OFQ) and its receptor, the opioid receptor-like 1 (NOP), remains unclear because this peptide has been implicated in both suppression and enhancement of nociception. The present work characterises the effects of N/OFQ and the NOP receptor antagonist, the pseudopeptide [Phe(1)Psi(CH(2)NH)Gly(2)]-nociceptin(1-13)-NH(2) (Phe(1)Psi), on thermonociception in the snail Helix aspersa using the hot plate assay. Additionally, the possible interaction of each of these compounds with morphine or dynorphin A(1-17) and naloxone was studied. Compounds were administered into the hemocoel cavity of H. aspersa and the latency to the aversive withdrawal behaviour recorded. Dose-response and time course curves were done. N/OFQ and naloxone produced a similar dose-dependent pronociceptive effect; however, N/OFQ reached its peak effect earlier and was 30 times more potent than naloxone. [Phe(1)Psi(CH(2)NH)Gly(2)]-nociceptin(1-13)-NH(2) and the opioid agonists, morphine and dynorphin A(1-17) produced antinociception with a similar efficacy, but [Phe(1)Psi(CH(2)NH)Gly(2)]-nociceptin(1-13)-NH(2) reached its peak effect more rapidly and lasted longer than that of dynorphin A(1-17) and morphine. [Phe(1)Psi(CH(2)NH)Gly(2)]-nociceptin(1-13)-NH(2) was 50 times less potent than dynorphin A(1-17), but 30 times more potent than morphine. N/OFQ significantly reduced morphine and dynorphin A(1-17)-induced antinociception. Combined administration of low doses of [Phe(1)Psi(CH(2)NH)Gly(2)]-nociceptin(1-13)-NH(2) and morphine or dynorphin A(1-17) produced a potent antinociceptive effect. Sub-effective doses of naloxone and N/OFQ also synergised to produce pronociception. Data suggest that these two opioid classes regulate nociception through parallel systems. The H. aspersa model appears as a valuable experimental preparation to continue the study of these opioid receptor systems.
Miller-Pérez
Carolina
C
Laboratorio de Histología y Microscopía Electrónica, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría, Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan. México D.F., C.P. 14370, México.
Sánchez-Islas
Eduardo
E
Pellicer
Francisco
F
Rodríguez-Manzo
Gabriela
G
Cruz
Silvia L
SL
León-Olea
Martha
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004399:Dynorphins / Q000494:pharmacology; D006372:Helix, Snails / Q000502:physiology*; D006358:Hot Temperature; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D004399:Dynorphins; D009020:Morphine; D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C114149:nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-