Light and electron microscopic study of the distribution of substance P‐immunoreactive fibers and neurokinin‐1 receptors in the skin of the rat lower lip

Abstract

Cutaneous antidromic vasodilatation and plasma extravasation, two phenomena that occur in neurogenic inflammation, are partially blocked by substance P (SP) receptor antagonists and are known to be mediated in part by mast cell-released substances, such as histamine, serotonin, and nitric oxide. In an attempt to provide a morphological substrate for the above phenomena, we applied light and electron microscopic immunocytochemistry to investigate the pattern of SP innervation of blood vessels and its relationship to mast cells in the skin of the rat lower lip. Furthermore, we examined the distribution of SP (neurokinin-1) receptors and their relationship to SP-immunoreactive (IR) fibers. Our results confirmed that SP-IR fibers are found in cutaneous nerves and that terminal branches are observed around blood vessels and penetrating the epidermis. SP-IR fibers also innervated hair follicles and sebaceous glands. At the ultrastructural level, SP-IR varicosities were observed adjacent to arterioles, capillaries, venules, and mast cells. The varicosities possessed both dense core vesicles and agranular synaptic vesicles. We quantified the distance between SP-IR varicosities and blood vessel endothelial cells. SP-IR terminals were located within 0.23-5.99 microm from the endothelial cell layer in 82.7% of arterioles, in 90.2% of capillaries, and in 86.9% of venules. Although there was a trend for SP-IR fibers to be located closer to the endothelium of venules, this difference was not significant. Neurokinin-1 receptor (NK-1r) immunoreactivity was most abundant in the upper dermis and was associated with the wall of blood vessels. NK-1r were located in equal amounts on the walls of arterioles, capillaries, and venules that were innervated by SP-IR fibers. The present results favor the concept of a participation of SP in cutaneous neurogenic vasodilatation and plasma extravasation both by an action on blood vessels after binding to the NK-1r and by causing the release of substances from mast cells after diffusion through the connective tissue.

Parasympathetic nerve fibers invade the upper dermis following sensory denervation of the rat lower lip skin

“…2A). These observations reproduced our previous results using the same anti-SP antibody in rat lip tissue (Ruocco et al, 2001a).…”

Sensory neuron and substance P involvement in symptoms of a zymosan-induced rat model of acute bowel inflammation

“…Thus, in addition to CGRP, substance P, released from peripheral terminals of sensory neurons may also play a role in regulation of gut tissue. Substance P has been implicated in neurogenic inflammation in other tissues (Wong et al, 2003;Lundy and Linden, 2004;MeyerSiegler and Vera, 2004), and the proximity of substance P immunoreactive fibers to blood vessels and mast cells confirms the important role of substance P in neurogenic inflammation (Ruocco et al, 2001). The observation that CP-96,345 reduced the effects of zymosan suggests that substance P plays a destructive, rather than a protective, role in regulation of gut tissue and thus its role seems to be different from that of CGRP.…”

Kinetics of neuronal contribution during the development of a contact allergic reaction

“…Substance P and NKA have an agonizing eVect on preferentially neurokinin-1 (NK-1) receptor (R) and NK-2R, respectively [14,15]. Both NK-1 and NK-2 receptors belong to the superfamily of G protein-coupled membrane receptors (GPCRs) [1].…”