Multiple interactions of unsaturated fatty acids with opiate and ouabain binding sites and beta-adrenergic sensitive adenylate cyclase system.
The unsaturated fatty acids oleic, linoleic and arachidonic inhibited binding of ligands to the ouabain, opiate, and beta-adrenergic plasma membrane receptors. Low concentrations of fatty acids slightly increased the binding of ouabain to its binding sites. The effect of these fatty acids on beta-adrenergic sensitive adenylate cyclase was more complex. 0.2-0.3 mM fatty acids increased adenylate cyclase activity, while higher concentrations of arachidonic and linoleic acids, but not oleic acid, inhibited basal, beta-agonist- and NaF-stimulated activities in membranes of A431 and C6 cells. To evaluate which aspects of the unsaturated fatty acid molecules might be responsible for the observed effects, myristic acid, monoolein and taurodeoxycholic acid were studied. They also inhibited binding to the opiate receptor. Myristic acid, did not inhibit ouabain binding, binding to beta-receptor, nor adenylate cyclase activity. Monoolein, had no inhibitory effect on ouabain binding but behaved similar to oleic acid in the beta-receptor/adenylate cyclase system. Taurodeoxycholic acid inhibited binding to all three receptors as well as adenylate cyclase activity. We conclude that the effects of unsaturated fatty acids on ligand binding and adenylate cyclase activity are the result of their multiple interactions with various molecular processes rather than any unique property of long chain unsaturated fatty acids, per se.
Xu
H
H
Laboratory of Theoretical and Physical Biology, National Institutes of Child Health and Human Development, Bethesda, MD 20892.
Lichtstein
D
D
Kassis
S
S
Lutz
R A
RA
Rodbard
D
D
Chernick
S S
SS
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D008560:Membrane Fluidity / Q000187:drug effects; D010042:Ouabain / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D011955:Receptors, Drug / Q000187:drug effects* / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013501:Surface-Active Agents / Q000494:pharmacology*
D005231:Fatty Acids, Unsaturated; D011943:Receptors, Adrenergic, beta; D011955:Receptors, Drug; D011957:Receptors, Opioid; D013501:Surface-Active Agents; C028996:cardiac glycoside receptors; D010042:Ouabain; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase