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Khalafalla MG, Woods LT, Jasmer KJ, et al. P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction. Front Pharmacol. 2020;11:222doi: 10.3389/fphar.2020.00222.
Khalafalla, M. G., Woods, L. T., Jasmer, K. J., Forti, K. M., Camden, J. M., Jensen, J. L., Limesand, K. H., Galtung, H. K., & Weisman, G. A. (2020). P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction. Frontiers in pharmacology, 11222. https://doi.org/10.3389/fphar.2020.00222
Khalafalla, Mahmoud G, et al. "P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction." Frontiers in pharmacology vol. 11 (2020): 222. doi: https://doi.org/10.3389/fphar.2020.00222
Khalafalla MG, Woods LT, Jasmer KJ, Forti KM, Camden JM, Jensen JL, Limesand KH, Galtung HK, Weisman GA. P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction. Front Pharmacol. 2020 Mar 13;11:222. doi: 10.3389/fphar.2020.00222. eCollection 2020. PMID: 32231563; PMCID: PMC7082426.
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Front Pharmacol. 2020 Mar 13;11:222. doi: 10.3389/fphar.2020.00222. eCollection 2020.

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction.

Frontiers in pharmacology

Mahmoud G Khalafalla, Lucas T Woods, Kimberly J Jasmer, Kevin Muñoz Forti, Jean M Camden, Janicke L Jensen, Kirsten H Limesand, Hilde K Galtung, Gary A Weisman

Affiliations

  1. Department of Biochemistry, University of Missouri, Columbia, MO, United States.
  2. Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, United States.
  3. Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
  4. Institute of Clinical Dentistry, Section of Oral Surgery and Oral Medicine, University of Oslo, Oslo, Norway.
  5. Department of Nutritional Sciences, University of Arizona, Tucson, AZ, United States.
  6. Institute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.

PMID: 32231563 PMCID: PMC7082426 DOI: 10.3389/fphar.2020.00222

Abstract

Although often overlooked in our daily lives, saliva performs a host of necessary physiological functions, including lubricating and protecting the oral cavity, facilitating taste sensation and digestion and maintaining tooth enamel. Therefore, salivary gland dysfunction and hyposalivation, often resulting from pathogenesis of the autoimmune disease Sjögren's syndrome or from radiotherapy of the head and neck region during cancer treatment, severely reduce the quality of life of afflicted patients and can lead to dental caries, periodontitis, digestive disorders, loss of taste and difficulty speaking. Since their initial discovery in the 1970s, P2 purinergic receptors for extracellular nucleotides, including ATP-gated ion channel P2X and G protein-coupled P2Y receptors, have been shown to mediate physiological processes in numerous tissues, including the salivary glands where P2 receptors represent a link between canonical and non-canonical saliva secretion. Additionally, extracellular nucleotides released during periods of cellular stress and inflammation act as a tissue alarmin to coordinate immunological and tissue repair responses through P2 receptor activation. Accordingly, P2 receptors have gained widespread clinical interest with agonists and antagonists either currently undergoing clinical trials or already approved for human use. Here, we review the contributions of P2 receptors to salivary gland function and describe their role in salivary gland dysfunction. We further consider their potential as therapeutic targets to promote physiological saliva flow, prevent salivary gland inflammation and enhance tissue regeneration.

Copyright © 2020 Khalafalla, Woods, Jasmer, Forti, Camden, Jensen, Limesand, Galtung and Weisman.

Keywords: Sjögren’s syndrome; extracellular nucleotides; head and neck cancer; purinergic receptors; saliva; salivary gland dysfunction

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