Head group and structure specific interactions of enkephalins and dynorphin with liposomes: Investigation by hydrophobic photolabeling

Abstract

The interaction of the opioid enkephalins and endorphins with lipid bilayers is largely unknown. Such interactions might, however, be important for understanding the molecular mechanisms of biological action. We have therefore studied the interaction of several enkephalins and of dynorphin-(1–13)-tridecapeptide (dynorphin 1–13) with model membrane systems, using the extremely hydrophobic photolabel of J. Brunner and G. Semenza, ( Biochemistry, 20, 7174–7182 (1981)) 3-trifluoromethyl-3-( m[ 125I]iodophenyl) diazirine. By observing several limitations of the method, it was possible to characterize hydrophobic interactions of opioid peptides with liposomes prepared from egg yolk phosphatidylcholine (PC) plus dipalmitoylphosphatidic acid (PA), from brain phosphatidylserine (PS) alone, and from brain cerebroside sulfate (CS) alone, Dynorphine 1–13 exhibited strong hydrophobic interactions through its N-terminal “message” segment which were potentiated by the “address” that itself remained in the aqueous phase. This behavior was consistent with the reported pharmacological potentiation. The enkephalins were generally weakly labeled in the PC PA and PS systems. However, in the CS systems the preferentially μ agonists were labeled very strongly whereas the preferentially δ agonists were labeled more weakly yet. The κ agonist, dynorphin 1–13, was strongly, but more equally labeled in the three systems. Thus, there was a head group specificity that, in our series of compounds, correlated with opiate receptor sub-type specificity. The results were consistent with the behavior of the μ agonist, morphine.