In vivo injection of antibodies directed against the cloned mu opioid receptor blocked supraspinal analgesia induced by mu-agonists in mice.
The intracerebroventricular (i.c.v.) injection to mice of a polyclonal antibody raised against the peptide sequence 208-216 (TKYRQGSID) of cloned rat mu opioid receptor, reduced the analgesic potency of DAMGO, morphine and beta-endorphin-(1-31) when studied 48 h later in the tail-flick test. Antinociception elicited by delta agonists, DPDPE and [D-Ala2]-Deltorphin II, and by the kappa agonist U-50488H, was fully expressed in mice undergoing this treatment. The specific binding displayed by 0.6 nM [3H]-DAMGO was reduced in membranes preincubated with the antiserum, whereas no change could be detected for 3 nM [3H]-DPDPE or 2 nM [3H]-U-69593 labelling delta and kappa opioid receptors respectively. Naloxonazine, irreversible antagonist of the pharmacologically defined mu 1 opioid receptor, and beta-funaltrexamine (beta-FNA), that also displays irreversible antagonism at mu 1/2 receptors, when injected i.c.v. 24 h before the opioids significantly reduced the activity of DAMGO and morphine. In mice treated with naloxonazine, but not with beta-FNA, the antibody further reduced the remaining analgesic effect of DAMGO and morphine. Thus, both the antibody and beta-FNA blocked a wider population of mu opioid receptors than that tagged by naloxonazine.
D000595:Amino Acid Sequence; D000698:Analgesia; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D044482:Benzeneacetamides; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000378:metabolism; D007116:Immunization, Passive; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009020:Morphine; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011759:Pyrrolidines / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000276:immunology / Q000502:physiology*; D001615:beta-Endorphin
D000906:Antibodies; D044482:Benzeneacetamides; D004745:Enkephalins; D010446:Peptide Fragments; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D001615:beta-Endorphin; D009020:Morphine; C034643:naloxonazine; D020881:Enkephalin, D-Penicillamine (2,5)-; C045444:U 69593