In vivo injection of antibodies directed against the cloned μ opioid receptor blocked supraspinal analgesia induced by μ-agonists in mice

摘要

The intracerebroventricular (i.c.v.) injection to mice of a polyclonal antibody raised against the peptide sequence 208-216 (TKYRQGSID) of cloned rat μ opioid receptor, reduced the analgesic potency of DAMGO, morphine and β-endorphin-(1-31) when studied 48 h later in the tail-flick test. Antinociception elicited by δ agonists, DPDPE and [D-Ala2]-Deltorphin II, and by the κ 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 δ and κ opioid receptors respectively. Naloxonazine, irreversible antagonist of the pharmacologically defined μ, opioid receptor, and β-funaltrexamine (β-FNA), that also displays irreversible antagonism at μ( 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 β-FNA, the antibody further reduced the remaining analgesic effect of DAMGO and morphine. Thus, both the antibody and β-FNA blocked a wider population of μ opioid receptors than that tagged by naloxonazine.