Calcium ionophoretic activity of chemically synthesized oligomeric derivatives of prostaglandin B1

• Published in: Biochimica et biophysica acta Vol. 924; no. 1; pp. 87 - 98
• Main Authors: Uribe, Salvador, Ohnishi, S.Tsuyoshi, Israelite, Craig, Devlin, Thomas M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 16.04.1987; North-Holland
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Calcium - metabolism; Fundamental and applied biological sciences. Psychology; Intracellular Membranes - drug effects; Intracellular Membranes - physiology; Ionophores - pharmacology; Kinetics; Lipids; Male; Membrane Potentials - drug effects; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Other biological molecules; Potassium - pharmacology; Prostaglandins - pharmacology; Prostaglandins B - chemical synthesis; Prostaglandins B - pharmacology; Rats; Rats, Inbred Strains; Sodium - pharmacology; Structure-Activity Relationship; Vertebrata; Mitochondria; Mammalia; Calcium; Rat; Arachidonic acid derivatives; Liver; Rodentia; Prostaglandin B1; Ionophore; Biological activity
• ISSN: 0304-4165; 0006-3002
• DOI: 10.1016/0304-4165(87)90074-2

Chemically synthesized dimers, trimers and tetramers of 15-dehydroprostaglandin B1 and 16,16'-dimethyl-15-dehydroprostaglandin B1 facilitate the release of Ca2+ from isolated rat liver mitochondria. The parent monomeric prostaglandins had no significant activity. The rate of release was stimulated by exogenous K+ or Na+, suggesting an antiport exchange of monovalent cations for intra-mitochondrial Ca2+. The activity depended upon the presence of ruthenium red, which prevented recycling of Ca2+; comparison of the activity with A23187 and carbonyl cyanide p-trifluoromethoxyphenylhydrazone indicated that the prostaglandin B1 oligomers were functioning as ionophores and the release of Ca2+ was not caused by an uncoupling of oxidative phosphorylation. The oligomers caused a major decrease in the membrane potential but only when the mitochondria were preloaded with exogenous Ca2+, and even then, the Ca2+ efflux was completed before the membrane potential decreased to less than 90 mV. The oligomeric molecules were able to form supramolecular aggregates in the presence of Ca2+ as detected by light scattering. They extracted Ca2+ into an organic phase, and translocated Ca2+ from one aqueous domain to another across an organic barrier; K+ and Na+ modulated these processes. The prostaglandin B1 derivatives also translocated Rb+ from one aqueous phase to another across an organic barrier when Ca2+ was translocated.