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 F 2α (PGF 2α ), resulted in a very rapid increase in the intracellular levels of [ 3 H]‐inositol triphosphate (IP 3 ), [ 3 H]‐inositol biphosphate (IP 2 ), and [ 3 H]‐inositol monophosphate (IP 1 ) in cells prelabeled with [ 3 H]‐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 PGF 2α . The cholinergic agent, carbachol, also led to time and dose‐independent increases in IP 3 . Lithium, cadmium, silver, copper, and zinc ions had no effect either on the breakdown of IP 3 or on the accumulation of IP 1 . In contrast, vanadate at 10 −6 or 10 −5 M did lead to a decrease in the breakdown of IP 1 and a concomitant increase in IP 1 , IP 2 , and IP 3 . PGF 2α was found previously to induce an increase in rabbit endometrial cell DNA synthesis which was inhibited by concomitant or prior addition of prostaglandin E 1 (PGE 1 ). PGE 1 , in a dose‐dependent manner, was found to inhibit the observed IP 3 increase by PGF 2α at 1 1/2 min of stimulation. PGF 2α treated and control cultures did not differ in cAMP or cGMP levels, cellular 45 Ca uptake, nor cellular 22 Na uptake. We propose that IP 3 may be one of the intracellular messenger(s) synthesized following the treatment of rabbit endometrial cell cultures with the proliferation agent PGF 2α and that it may play a crucial role with cAMP in growth regulation.