Direct membrane effects of morphine and endorphins on Amoeba proteus.
Morphine, leu-enkephalinamide, met-enkephalin, alpha-neoendorphin and its Arg8 1-8 fragment increase contractile vacuole output in the freshwater Amoeba proteus at 18 microM. Significant effects of leu-enkephalin and naloxone are obtained at 180 microM. All compounds have reached their maximal activity at 720 microM. Alpha-neoendorphin and leu-enkephalin are inactive in the presence of isotonic, non-penetration sucrose, hence these compounds increase plasma membrane permeability to water. Results from molecular modeling show a clear correlation of activity with amphiphilicity, charge distribution and general flexibility of molecules. We conclude that, like previously-studied vasopressin analogues and non-hormonal amphiphilic peptides, active opioids embed themselves into the Amoeba plasma membrane, disrupting the lipid bilayer and increasing its permeability. In our Amoeba system, naloxone, a general morphine-like inhibitor, blocks active opioids as well as a vasopressin analogue. Naloxone, being less active than other tested amphiphiles, acts as a membrane stabilizer, protecting the lipid bilayer against the disruption action of more active compounds.
Mayers
P
P
Département de Sciences Biologiques, Université de Montréal, Canada.
Couillard
P
P
D000656:Amoeba / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D004723:Endorphins / Q000494:pharmacology*; D008958:Models, Molecular; D009020:Morphine / Q000494:pharmacology*; D014617:Vacuoles / Q000378:metabolism / Q000502:physiology; D014867:Water
D004723:Endorphins; D014867:Water; D009020:Morphine