Sympathetic innervation stimulates β-adrenergic receptors, triggering cyclic adenosine monophosphate (cAMP) production and enhancing protein secretion in salivary gland cells. While cAMP signaling, in conjunction with Ca2+ signaling, is essential for salivary gland function, the identified cAMP-producing G-protein-coupled receptors (GPCRs) remains limited. Here, we report the presence of cAMP-producing adenosine receptors in salivary gland cells. By reanalyzing publicly available single-cell transcriptome datasets of human and mouse submandibular glands, we identified mRNA expression of adenosine A1, A2A, A2B, and A3 receptors. Additionally, we confirmed that 5’-N-ethylcarboxamidoadenosine (NECA), an adenosine A2B receptor agonist, increases cAMP levels in human salivary gland cells, suggesting a physiological role for adenosine A2B receptors. Our findings enhance understanding of adenosine’s regulatory function in salivary glands and highlight new avenues for research on cAMPproducing adenosine receptors.

Introduction
Materials and Methods
    1. Materials
    2. Cell culture
    3. Analysis of scRNA-seq data
    4. Determination of cAMP concentration
    5. Statistical analysis
Results
    1. Investigating adenosine receptor expression in thesalivary gland through reanalysis of scRNA-seqdatasets
    2. Adenosine receptor agonist NECA evokes cAMPproduction in human salivary gland cells
Discussion
Funding
Conflicts of Interest
References

• Ji-Ah Kang(Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul 03080, Republic of Korea)
• Yoo-Bin Kim(Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul 03080, Republic of Korea)
• Se-Young Choi(Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul 03080, Republic of Korea) Corresponding author
• Sunghan Lee(Department of Oral Medicine and Oral Diagnosis, Dental Research Institute, Seoul National University School of Dentistry, Seoul 03080, Republic of Korea)
• Hee-Kyung Park(Department of Oral Medicine and Oral Diagnosis, Dental Research Institute, Seoul National University School of Dentistry, Seoul 03080, Republic of Korea, Department of Oral Medicine, Seoul National University Dental Hospital, Seoul 03080, Republic of Korea) Corresponding author