Non-parenchymal cells as mediators of physiological responses in liver

Abstract

Parenchymal cells (hepatocytes) are the sites at which the principal metabolic functions of the liver are located. In the perfused liver, responses (e.g. vasoconstriction and glycogenolysis) to stimulating agents such as zymosan, platelet-activating factor and arachidonic acid, are inhibited by indomethacin and bromophenacyl bromide, inhibitors of cyclo-oxygenase and phospholipase A2, respectively. Since cultured Kupffer and endothelial cells but not hepatocytes, produce eicosanoids, and since eicosanoids and especially prostaglandins induce similar patterns of responses when added directly to the perfused liver, an involvement of these non-parenchymal cells in mediating the above responses is considered likely. We propose that in most situations the responses induced by these stimulating agents are mediated through a combination of pathways that include interaction of the agents directly with hepatocytes or with vasoactive cells (endothelial and/or smooth muscle cells), or interaction of agents initially with non-parenchymal cells to produce and release eicosanoids, which then subsequently interact with hepatocytes or with vasoactive cells.

Dietary juniper berry oil minimizes hepatic reperfusion injury in the rat

“…9 By preventing the formation of deleterious eicosanoids, fish oil treatment also decreases vasoconstriction and subsequent microcirculatory failure. In support of this idea, it was demonstrated here that juniper berry oil prevented activation of Kupffer cells and minimized production of the vasoactive eicosanoid, PGE 2 (Fig. 10).…”

“…Kupffer cells are the major source of eicosanoids in the liver. 2 Therefore, production of PGE 2 , a vasoactive eicosanoid, 28 was measured in cultured Kupffer cells. After lipopolysaccharide (10 µg/mL) stimulation, PGE 2 levels in culture media increased by 152% (Fig.…”

“…It is well known that Kupffer cells are the major source of eicosanoids in the liver. 2 Arachidonic acid derived from linoleic acid in corn oil serves as a substrate for the formation of eicosanoid mediators, and many of these mediators are known to be vasoactive, such as PGE 2 20:4 6. 9,21,22 Furthermore, juniper berry oil has been shown to replace arachidonic acid more rapidly than fish oil.…”

Calcium: its modulation in liver by cross-talk between the actions of glucagon and calcium-mobilizing agonists

“…As mentioned above, Altin and Bygrave (1986) observed that following coadministration of glucagon and vasopressin to perfused rat livers, Ca2+ outflow was unaffected but Ca2+ inflow was greatly enhanced. Finally, and again using the Ca2+-electrode and 45Ca techniques, Altin and Bygrave (1987c) were able to demonstrate in the perfused rat liver that the main effect of these hormones was to activate a Ca2+ inflow pathway rather than to inhibit Ca2+ outflow via the Ca2+-ATPase. On the other hand, a recent study has concluded that dibutyryl cyclic AMP stimulates Ca2+ efflux in rat hepatocytes (F. L. Bygrave, A. Gamberucci, R. Fulceri, R. Giunti and A. Benedetti, unpublished work).…”

Induction of haemodynamic oscillations in the perfused rat liver by K+ channel blockers.

“…Resistance to blood flow within the liver is controlled by a variety of hormonal and non-hormonal substances which are released by intrahepatic nerve endings and nonparenchymal cells or borne by blood from extrahepatic sources (Beckh, Balks & Jungermann, 1982;Altin & Bygrave, 1988;Ballet, 1990; Bioulac-Sage, Lafon, Saric & Balabaud, 1990). Although the haemodynamic responses to supraphysiological concentrations of these substances are well characterized, the cellular and molecular aspects of intrahepatic haemodynamic control is unclear.…”