Intralobular innervation and lipocyte contractility in the liver

In the liver of humans, guinea pigs, cats, and tupaia, nerve endings are distributed all over the hepatic lobules from the portal spaces to the centralobular spaces. Nerve endings in the intralobular spaces are located mainly in the space of Disse, and are closely related to lipocytes. In the human liver, various neurotransmitters such as substance P (SP) exist in the nerve endings. Lipocytes are believed to contract through these substances. In fact, the contraction of lipocytes is induced by SP. Moreover, lipocytes possess endothelin (ET) receptors (ETA, ETB), and the cells are contracted by ET-1 by way of ET receptors in the autocrine or paracrine mechanism. Contraction of lipocytes seems to be related to the enhancement of the intracellular Ca2+ and inositol phosphates. In addition, α-smooth muscle actin, which is a contractile protein, exists in the cytoplasm of lipocytes. Lipocyte contractility may be similar to that of vascular smooth muscle cells. On the other hand, prostaglandin E2, Iloprost, and adrenomedullin cause the elevation of c-AMP levels in lipocytes and relax the cells. In addition, lipocytes produce nitric oxide (NO) and inhibit contractility by an autocrine mechanism related to NO. In this way, lipocytes appear to be associated with the regulation of hepatic sinusoidal microcirculation by contraction and relaxation. In the cirrhotic liver, intralobular innervation is decreased or absent, but ET-1 and NO are overexpressed. These phenomena indicate that lipocytes may play an important role in the sinusoidal microcirculation through these agents rather than through intralobular innervation in liver cirrhosis.