The effects of exposure to unsaturated fatty acids on opiate receptors, prostaglandin E₁ receptors, and adenylate cyclase activity of neuroblastoma x glioma hybrid cells

The effects of alterations in membrane fatty acid composition on receptors for opiates and prostaglandin E₁ (PGE₁) and on the activity of adenylate cyclase were studied in clonal neuroblastoma x glioma hybrid cells (NG108-15) following exposure to unsaturated fatty acids. Decreases in binding of [³H]etorphine and [³H]PGE₁ were observed in cells exposed to arachidonate (20:4), linoleate (18:2), and oleate (18:1). The observed decreases in binding (as much as 80% decrease under some conditions) were primarily associated with changes in the number of binding sites. The effects of 20:4 and 18:2 were more rapid and greater than those of 18:1. The decreases in binding approximately paralleled the time (6-72 hr) and concentration-dependent enrichment of the membranes with the exogenously supplied fatty acids. However, when 20:4-treated cells were switched to normal culture medium the number of binding sites returned to control values much more rapidly than did the phospholipid fatty acid composition. This observation suggests that decreases in receptor number were a result of changes occurring during the pretreatment with fatty acids (e.g., a decrease in receptor synthesis, a decrease in receptor insertion into the membranes, or increased removal of the receptor from the membranes); the apparent number of receptors was not determined by the membrane fatty acid composition at the time binding was measured. In contrast, the adenylate cyclase activity of the cells was unaffected by even very large changes in phospholipid fatty acid composition. Likewise, the regulatory response to chronic exposure of the cells to PGE₁ (decreases in both PGE₁ receptors and adenylate cyclase activity) was not affected by simultaneous exposure to PGE₁ and 20:4. Thus, the number of opiate and PGE₁ receptors was selectively altered by exposure of the cells to unsaturated fatty acids.