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The localization of neuropeptide Y (NPY)-, substance P (SP)- and calcitonin gene-related peptide (CGRP)-containing nerve fibers around lymphatic capillaries (initial lymphatics) in the interlobular connective tissue of the rat liver was investigated by preembedding immunoelectron-microscopy. Nerve terminals with NPY were frequently seen in close apposition to the abluminal surface of lymphatic endothelium. A small number of NPY fibers without a glial (Schwann cell) covering at the tip ran toward lymphatic capillaries in the interlobular connective tissue. Nerve fibers immunoreactive for SP were present within unmyelinated fiber bundles that ran close to lymphatic capillaries in the interlobular connective tissue. Besides these immunoreactive nerve fibers, many of which appeared to pass through the subendothelial regions of lymphatic capillaries, scattered SP nerve endings were seen in areas contiguous to lymphatic endothelium. CGRP terminals were rarely found around lymphatic capillaries, although nerve fiber bundles containing CGRP components traversed close to some lymphatic capillaries. These findings suggest that NPY and SP, if released from nerve terminals into the subendothelial areas of adjacent lymphatic capillaries, are more likely to affect the metabolic activity of lymphatic endothelium and the flow (or formation) of lymph than CGRP. SP and CGRP, as possible mediators of sensory transmission, might be involved in the conveyance of information on the hydrostatic pressures of hepatic lymphatics and surrounding tissue fluid to the central nervous system.

Immunoelectron-microscopic localization of peptidergic nerve fibers around lymphatic capillaries in the rat liver.