Opioid properties of β-lipotropin fragment 60-65, HArgTryGlyGlyPheMetOH

The pharmacologic activity of the hexapeptide fragment corresponding to the amino acid fragment 60-65 in β-lipotropin, (β-LPH-(60-65)) was studied in vitro and in vivo. In binding assays on synaptosomal plasma membrane the peptide was found to be equipotent to met-enkephalin, but behaved differently to cations; in contrast to met-enkephalin both Mn⁺² and Na⁺ enhanced the binding of β-LPH-(60-65) to synaptosomal plasma membrane. On both the quinea pig ileum and mouse vas deferens β-LPH-(60-65) inhibited contractions elicited by electrical stimulation and each effect was reversible by naloxone. On the guinea pig ileum β-LPH-(60-65) was equipotent to met-enkephalin and 0.5 as potent as normorphine but on the vas deferens it was 4.6 times more potent than normorphine. The activities of β-LPH-(60-65) appear to be due to the intact compound rather than to its conversion to met-enkephalin, since the peptide extracted from the ileum assay was found to behave identically as β-LPH-(60-65) with high pressure liquid chromatography. When β-LPH-(60-65) was administered centrally to mice and rats, no overt central actions were observed and an antinociceptive effect could not be demonstrated. Nor did β-LPH-(60-65) antagonize morphine action or precipitate the withdrawal syndrome in morphine dependent animals. It is concluded that the good agreement which generally exists between in vitro and in vivo assay procedures for opiate-like activity of morphine and its surrogates does not necessarily hold for the endogenous peptides with similar actions.