# Neuronal nitric oxide synthase expression in secretory cells of the human parotid and submandibular salivary glands: evidence from light and electron microscopy

**Authors:** Michela Isola, Marianna Boi, Roberto Demontis, Raffaella Isola, Francesco Loy, Cristina Maxia, Daniela Murtas, Maria Pina Serra, Jörgen Ekström, Marina Quartu

PMC · DOI: 10.1007/s00441-026-04048-7 · Cell and Tissue Research · 2026-02-13

## TL;DR

This study identifies where neuronal nitric oxide synthase is located in human salivary glands, showing it is present in secretory and ductal cells but not in mucous cells.

## Contribution

The study provides the first ultrastructural evidence of nNOS in human salivary gland secretory and ductal cells.

## Key findings

- nNOS is localized in serous secretory cells and ductal epithelium of parotid and submandibular glands.
- Ultrastructural analysis shows nNOS in secretory granules, vesicles, and various cellular compartments of ductal cells.
- Mucous cells show no nNOS immunoreactivity, and nitrergic nerve fibers are rare in gland tissue.

## Abstract

Nitric oxide plays a crucial role in multiple physiological processes in salivary glands, yet its precise cellular sources in human glandular tissues remain insufficiently characterized. This study investigated the distribution and subcellular localization of neuronal nitric oxide synthase (nNOS) in human parotid and submandibular gland tissue samples obtained from surgical biopsies and autopsies, using both light and electron-microscope immunohistochemistry. In both gland types, nNOS was consistently observed in serous secretory cells and the ductal epithelium, whereas mucous cells showed no immunoreactivity. Ductal cell staining was heterogeneous, with some cells displaying intense labeling and others remaining unstained. Nerve fibers containing the enzyme were rare within the gland parenchyma. Ultrastructural analysis revealed the enzyme within secretory granules and small cytoplasmic vesicles of serous cells, as well as in the apical and basal cytoplasm, mitochondria, and nuclei of ductal epithelial cells. These findings provide the first ultrastructural evidence of nNOS in secretory and ductal cells of human major salivary glands. The selective localization in serous cells, absence in mucous cells, and limited nitrergic innervation suggest a substantial parenchymal contribution to nitric oxide production. This distribution indicates that nitric oxide regulates saliva formation, composition, and intracellular signaling and could play a broader role in oral physiology and disease.

## Linked entities

- **Proteins:** NOS1 (nitric oxide synthase 1)
- **Chemicals:** nitric oxide (PubChem CID 145068)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** NOS1 (nitric oxide synthase 1) [NCBI Gene 4842] {aka IHPS1, N-NOS, NC-NOS, NOS, bNOS, nNOS}
- **Chemicals:** Nitric oxide (MESH:D009569)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12904907