Comparison of the endogenous heptapeptide Met-enkephalin-Arg6-Phe7 bindingin amphibian and mammalian brain

In previous communications [4, 38] we published that [H-3]Met-enkephalin-Ar g(6)-Phe(7) (MERF) binds to opioid (kappa(2) and delta) and sigma(2) sites in frog and rat brain membrane preparations, however no binding to kappa(1) sites could be established. In the present paper we compare the frog, rat and guinea pig brain membrane fractions with respect to their MERF binding data. No qualitative differences were found between the three species but s pecific binding of labelled MERF was maximal in frog brain and lowest in gu inea pig brain, which corresponds to their kappa(2) opioid receptor distrib ution. The naloxone resistant binding was also present in all investigated species and varied from 25% in frog and guinea pig cerebrum, to 50% in rat cerebrum and cerebellum, but no naloxone inhibition was found in guinea pig cerebellum where no kappa(2) opioid receptors have been found. The presenc e of sigma(2)-like receptor was demonstrated in each investigated membrane fraction with displacement experiments using (-)N-allyl-normetazocine as co mpetitor of tritiated MERF. It was shown that this site was responsible for 60-80% of [H-3]MERF binding. The remaining part of the naloxone resistant labelled MERF binding could be displaced only with endogenous opioid peptid es as met-enkephalin, dynorphin and beta-endorphin. The eventual physiologi cal role of multiple MERF receptors is discussed.