PROSTAGLANDIN-F2-ALPHA AND D-2 RELEASE FROM PRIMARY ITO CELL-CULTURES AFTER STIMULATION WITH NORADRENALINE AND ATP BUT NOT ADENOSINE

Rat liver Ito cells were cultured for 24 hr with 20% newborn calf serum. Stimulation with the sympathetic neurotransmitter noradrenaline (0.1 mu mol/L to 1 mmol/L) led to a dose-dependent increase in prostaglandin F-2 alpha release and a slightly smaller enhancement of prostaglandin D-2 production. Prostaglandin F-2 alpha and prostaglandin D-2 synthesis was highest in the first 30 sec after stimulation. Stimulation with the possible cotransmitter ATP (10 mu mol/L and 1 mmol/L ATP) also enhanced both prostaglandin F-2 alpha and prostaglandin D-2 release strongly. The release was highest again during the first 30 sec. Stimulation with noradrenaline and ATP simultaneously did not increase the effects of noradrenaline or ATP alone. Adenosine had no effect on prostaglandin production. The effects of noradrenaline were inhibited specifically by the alpha(1)-adrenoreceptor antagonist prazosin but not by the p(1)-purinoreceptor antagonist 8-phenyltheophylline. The effects of ATP were not antagonized by the inhibitors. Because the metabolic actions of sympathetic hepatic nerves can be inhibited by inhibitors of prostanoid synthesis and mimicked by prostaglandins F-2 alpha and D-2, and because the Ito cells are well innervated, our results permit the conclusion that Ito cells could be involved in the nervous signal chain: During sympathetic nerve action the neurotransmitter noradrenaline and the cotransmitter ATP cause increases in prostaglandin F-2 alpha and prostaglandin D-2 release from Ito cells within 30 to 60 sec by way of alpha(1) and p(2) receptors, respectively. The released prostaglandins then activate glycogenolysis in the hepatocytes proper.