Regulation of opioid antagonist and mu, kappa or delta agonist binding by guanine nucleotide and sodium.

Effects of 5'-guanylylimidodiphosphate (Gpp(NH)p) and sodium on the inhibition by various opioids of [3H]-naloxone binding to guinea-pig brain membrane preparations were studied. The ratio of the concentration required to produce a 50% inhibition of [3H]-naloxone binding in the presence of both Gpp(NH)p and sodium to that in the absence of both Gpp(NH)p and sodium (IC50 ratio) was less than 1 for antagonists, from 3 to 10 for mixed agonist-antagonists, from 16 to 85 for either kappa, delta, or peptide mu agonists, and more than 200 for morphine-like nonpeptide mu agonists. Exceptionally, the IC50 ratio of N,N-diallyl-[D-Ala2,D-Leu5]-enkephalin, an opioid which had been shown not to have an agonist activity in guinea-pig ileum but to have a naloxone-reversible agonist activity in mouse vas deferens, was less than 1. The significance of the different IC50 ratio among opioids employed in the present study was discussed.