Selective involvement of kappa opioid and phencyclidine receptors in the analgesic and motor effects of dynorphin-A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro.
Dynorphin A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro (Dyn Ia; 1-8 nmol) injected intracerebroventricularly in the mouse produces two independent behavioral effects: (1) a norbinaltorphimine (kappa opioid antagonist)-reversible analgesia in the acetic acid-induced writhing test and (2) motor dysfunction characterized by wild running, pop-corn jumping, hindlimb jerking and barrel rolling and antagonized by the irreversible phencyclidine (PCP) and sigma (sigma) receptor antagonist, metaphit and the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, dextromethorphan and ketamine. The specific involvement of the PCP receptor in the motor effects of Dyn Ia is supported by the direct competitive interaction of the peptide with the binding of [3H]MK-801 (Ki: 0.63 microM) and [3H]TCP (Ki: 4.6 microM) to mouse brain membrane preparations.
Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ont., Canada.
V K
VK
Shukla
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Bansinath
M
M
Dumont
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S
Lemaire
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004399:Dynorphins / Q000031:analogs & derivatives* / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects*; D011869:Radioligand Assay; D017473:Receptors, Opioid, kappa / Q000502:physiology*; D017478:Receptors, Phencyclidine / Q000502:physiology*
D000700:Analgesics; D017473:Receptors, Opioid, kappa; D017478:Receptors, Phencyclidine; C070405:dynorphin A (1-13), Tyr(14)-Leu(15)-Phe(16)-Asn(17)-Gly(18)-Pro(19)-; D016291:Dizocilpine Maleate; D004399:Dynorphins