Regulation of inositol phosphate levels by prostaglandins in cultured endometrial cells.

Stimulation of cultured rabbit endometrial cells by one of the rabbit endometrial cell culture proliferation factors, prostaglandin F2 alpha (PGF2 alpha), resulted in a very rapid increase in the intracellular levels of [3H]-inositol triphosphate (IP3), [3H]-inositol biphosphate (IP2), and [3H]-inositol monophosphate (IP1) in cells prelabeled with [3H]-inositol. These increases in inositol phosphate levels were detected in periods of stimulation as short as 30 seconds, reached a maximum by 1 1/2-2 min and declined to control levels by 6-10 min. The stimulation was dose-dependent with maximal increases observed near 10(-6) M PGF2 alpha. The cholinergic agent, carbachol, also led to time and dose-independent increases in IP3. Lithium, cadmium, silver, copper, and zinc ions had no effect either on the breakdown of IP3 or on the accumulation of IP1. In contrast, vanadate at 10(-6) or 10(-5) M did lead to a decrease in the breakdown of IP1 and a concomitant increase in IP1, IP2, and IP3. PGF2 alpha was found previously to induce an increase in rabbit endometrial cell DNA synthesis which was inhibited by concomitant or prior addition of prostaglandin E1 (PGE1). PGE1, in a dose-dependent manner, was found to inhibit the observed IP3 increase by PGF2 alpha at 1 1/2 min of stimulation. PGF2 alpha treated and control cultures did not differ in cAMP or cGMP levels, cellular 45Ca uptake, nor cellular 22Na uptake. We propose that IP3 may be one of the intracellular messenger(s) synthesized following the treatment of rabbit endometrial cell cultures with the proliferation agent PGF2 alpha and that it may play a crucial role with cAMP in growth regulation.