Nitric oxide synthase in human salivary glands

Abstract

The distribution of the three nitric oxide synthase (NOS) isoforms was determined immunohistochemically in the human minor and major salivary glands with comparison to that of rat salivary glands. In contrast to rat glands, which contained a dense plexus of neuronal NOS-immunoreactive nerve fibers, only a minority of the nerve fibers in human glands showed neuronal NOS immunoreactivity. Human labial and submandibular glands contained sparse NOS-immunoreactive fibers, while only occasional nerve fibers in the parotid or sublingual glands were stained. Furthermore, in contrast to the animal glands, most duct epithelial cells in all human salivary glands were immunoreactive for neuronal NOS. No specific immunoreactivity for inducible or endothelial NOS were observed in the nerve fibers or duct epithelium. We provide evidence to suggest that the role of nitric oxide in the regulation of salivary gland function is different in human as compared to experimental animals. Nitricergic innervation in human tissue is very sparse and thus nitric oxide is probably of minor importance as a neural regulator of salivary glands. Instead, NOS localized in duct epithelial cells suggests that nitric oxide might directly regulate saliva secretion and it is a putative source of nitrates previously reportedly secreted into the saliva.

Immunohistochemical characterisation of neurons in the mandibular ganglion and nerve fibres supplying the porcine mandibular gland

“…In the human MGl (Soinila et al 2006), nerve endings immunoreactive to VIP, GAL or NPY supplying the mucous acini have been found to be significantly more numerous than those apposing the serous acini. Furthermore, Del Fiacco et al (2014) have revealed that besides VIP-positive axons, also PHM-immunoreactive nerve terminals found in close proximity to acini and ducts are relatively abundant in the human MGl.…”

“…Immunoreactivity to nNOS has been found in a few nerve fibres supplying human, rat, cat and ferret salivary glands (Lohinai et al 1995;Alm et al 1997;Takai et al 1999;Soinila et al 2006). In the ferret and rat, NOS-positive varicose nerve terminals encircled the glandular acini and arteries of various sizes (Alm et al 1997).…”

“…In humans, in contrast to the rat glands, which contained a dense plexus of NOS-positive nerve fibres, only solitary NOS-immunoreactive nerve terminals are encountered (Soinila et al 2006). These authors have suggested that in humans NO plays a minor role as a neuronal regulator of saliva synthesis and excretion because this substance is expressed by only a small number of nerve fibres supplying the salivary gland tissue.…”

“…In humans, also only a relatively small number of SP-and CGRP-positive nerve endings were observed to be associated with the mucous and serous acini (Salo et al 1993;Kusakabe et al 1997;Soinila et al 2006). In the rat MGl, varicose CGRP-positive nerve fibres were located around interlobular salivary ducts and small blood vessels.…”

Mechanisms of Salivary Gland Secretory Dysfunction in Sjögren’s Syndrome

“…Surprisingly, immunohistochemical analyses of human minor and major salivary glands revealed that nNOS is strongly restricted to the non-neuronal duct epithelium and only a minority of the major salivary gland nerve fibers (surrounding acini, tubuli, ducts and blood vessels) expressed nNOS (Soinila, Nuorva, and Soinila 2006). In addition, salivary gland acinar cells have been demonstrated to express NOS (Looms et al 2002, ;Looms et al 2000, ;Soinila, Nuorva, and Soinila 2006). Human labial salivary gland acinar cells possess NOS activity and exhibit a very low level of NO production without stimulation in vitro (Looms et al 2000).…”