Effects of prostaglandin on substrate uptake and cell division in human diploid fibroblasts

Abstract

PG (prostaglandin) El inhibits the uptake of uridine, thymidine, 2-deoxy-D-glucose and L-isoleucine into human diploid WI38 fibroblasts. The inhibition occurs within seconds of the addition of the prostaglandin to the culture. PGE2, PGFlm and PGF2. behave similarly. Arachidonic acid and 8,11,14-eicosatrienoic acid also decrease uptake in the presence or absence of indomethacin. Other unsaturated fatty acids such as oleic acid, linoleic acid and linolenic acid are essentially inactive. Ricinoleic acid (the 9-hydroxyoleic acid), however, inhibits uptake to about the same degree, at concentrations similar to those of the prostaglandins. Results indicate that this rapid blockage by the prostaglandins and certain fatty acids is not cyclic AMP-mediated. For example, although PGF1, and PGF2. are much poorer stimulators of cyclic AMP formation than are PGE1 and PGE2, they are nevertheless effective inhibitors of substrate uptake. Adrenaline, a very effective stimulator of cyclic AMP formation in the cells, is not inhibitory. Also, the addition of 8-methylthioadenosine 3': 5'-cyclic monophosphate (methylthio cyclic AMP) to the culture does not cause an immediate blockage of uptake. However, 22h after addition to the culture, methylthio cyclic AMP decreases the uptake of nucleotides into cultures undergoing active cell division, approximately to values found in quiescent cultures. PGE1 also has this effect on cells undergoing active growth. This gradual decrease in substrate uptake caused by PGE1 appears to be a separate event from its initial rapid inhibition of uptake.

Collagen lattice effects on fibroblast arachidonic acid metabolism

“…Much of the metabolism of arachidonic acid in cell populations is probably not basal but occurs in response to specific extracellular signals a t the cell surface. Earlier reports have shown that the state of proliferation and confluence of the fibroblast influences its response to the hormone agonist bradykinin (Taylor and Polgar, 1981;Whiteley and Needleman, 1984) and that the PGE2 released in turn causes a decrease in the proliferation of the fibroblast (Taylor and Polgar, 1977;Polgar and Taylor, 1977). Since the matrix-embedded cells are nonproliferative but still nonconf luent, examining whether the stimulated responses of these cells resemble those of confluent fibroblasts may aid in the interpretation of data obtained from cells grown on plastic.…”

Final Report on the Safety Assessment of Ricinus Communis (Castor) Seed Oil, Hydrogenated Castor Oil, Glyceryl Ricinoleate, Glyceryl Ricinoleate SE, Ricinoleic Acid, Potassium Ricinoleate, Sodium Ricinoleate, Zinc Ricinoleate, Cetyl Ricinoleate, Ethyl Ricinoleate, Glycol Ricinoleate, Isopropyl Ricinoleate, Methyl Ricinoleate, and Octyldodecyl Ricinoleate1

“…At a concentration of 50 μM, Ricinoleic Acid suppressed the uptake of uridine into human diploid fibroblasts in culture (Polgar and Taylor 1977).…”