Prostaglandin F2α and D2 release from primary ito cell cultures after stimulation with noradrenaline and ATP but not adenosine

Abstract

Rat liver Ito cells were cultured for 24 hr with 20% newborn calf serum. Stimulation with the sympathetic neurotransmitter noradrenaline (0.1 pmol/L to 1 mmoln) led to a dose-dependent increase in prostaglandin F,, release and a slightly smaller enhancement of prostaglandin D, production. Prostaglandin F,, and prostaglandin D, synthesis was highest in the first 30 sec after stimulation. Stimulation with the possible cotransmitter A W (10 pmol/L and 1 mmoln ATP) also enhanced both prostaglandin F,, and prostaglandin D, 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 noradrendine were inhibited specifically by the a,-adrenoreceptor antagonist prazosin but not by the p,-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,, and D,, 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 The liver is innervated by sympathetic and parasympathetic, afferent and efferent nerves (1-5). Stimulation of the perivascular nerve bundles in isolated perfused rat liver led to increases in glucose and lactate output (6,7),

The niche of stellate cells within rat liver

“…These prostaglandins activate the glycogenolysis in the neighboring parenchymal cells. 37 These findings indicate that the sympathetic nervous system may also be relevant for the HSC niche (Fig. 6).…”

Hepatic stem cell niches

“…Hepatic stellate cells can directly respond to perivascular nerve stimulation through the release of the osmolyte myoinositol and exhibit Ca 2+ transients in response to phenylephrine (112,113). Their stimulation with norepinephrine leads to a rapid release of prostaglandins, which can activate glycogenolysis in neighboring liver parenchymal cells (114,115), thereby increasing the local glucose concentration. Thus, stellate cells can integrate signals from distant cells or organs to affect the behavior of neighboring cells in their niche.…”

“…Quiescent stellate cells in turn secrete HGF, which is probably involved in liver tissue homeostasis and can support hepatic progenitor cells (75,76). HSCs receive signals from the sympathetic nervous system through norepinephrine (NE) release (112,115). environment in the space of Disse controls the behavior of stellate cells and represents their niche (Figure 2).…”

Nervous control of liver metabolism and hemodynamics

“…In addition, circulating noradrenaline had no effect on glucose or lactate output in concentrations that could be expected to result from release of noradrenaline from the nerve endings into the circulation. The hypothesis that the metabolic effects of nerve stimulation were a mere consequence of an impaired sinusoidal circulation resulting in hepatocellular hypoxia could be dismissed, since the nerve-stimulation-elicited increase in glucose and lactate output remained nearly unaffected when the flow reduction was prevented by sodium nitroprusside [73,971 or nifedipine [98]. Similarly, the nerve-stimulation-dependent formation of ketone bodies [78,88], allantoin and uric acid [76], conjugation of xenobiotics [80] and secretion of bile [81] were independent of flow changes in contrast to the changes in urea, glutamine and ammonia balance [79] (not shown).…”