The effect of λ-type endorphins on α-MSH release in the rat

Abstract Neuroleptic drugs increase the level of α-melanotropin (α-MSH) in the blood of the rat. We have investigated whether neuroleptic-like peptides, the γ-type endorphins, also affect α-MSH release. A structure-activity study revealed that (des-enkephalin)-γ-endorphin (DEγE, β-LPH-(66–77), β-endorphin-(6–17)) is able to increase plasma α-MSH levels after intracerebroventricular injection, while the longer γ-type endorphins, i.e. γE (β-LPH-(61–77)), β-endorphin-(1–17)), and DTγE (β-LPH-(62–77), β-endorphin-(2–17)) were without effect in the dosage used. A dose-response study revealed a more or less bell-shaped relationship for the effect of DEγE on plasma α-MSH levels. The effect of DEγE could not be counteracted by apomorphine or naloxone. The observations indicate that DEγE increases plasma α-MSH levels in a way distinct from that of haloperidol and the opiate peptide β-endorphin. On the other hand, a time-course of plasma α-MSH levels after DEγE administration resembled the one which has been seen after haloperidol injection. From experiments performed on pituitary neurointermediate lobes incubated in vitro , it seems not likely that DEγE acts directly on the dopamine receptors of the pituitary in affecting α-MSH release. In conclusion, it appears that DEγE affects α-MSH levels in plasma in a way distinct from that of the neuroleptic drug haloperidol and of the opiate-peptide β-endorphin.