Aziz Eftekhari 1, Mohammad Samiei 2, Elham Ahmadian 3,4*
1 Pharmacology and Toxicology department, Maragheh University of Medical Sciences, Maragheh, Iran
2 Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
3 Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4 Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
*Corresponding authors:
Elham Ahmadian: Tabriz University of Medical Sciences, Tabriz, Iran. Email: ahmadian.elham@yahoo.com. Tel: +98 9144454094
Abstract
One of the main factors in cell function and tissue homeostasis is communication between the cell and the extracellular environment via pannexin channels (Panxs) or connexin hemichannels. The dentin structure and the function of the intra-dental nerves are influenced in dentinal hypersensitivity and if left untreated it can turn into a chronic inflammation in dentin, pulp and periodontal tissues. In this review, we will highlight the latest reports on the role of pannexin channels in oral health especially in the treatment of inflammation in dentin, pulp, and periodontal tissues. The reviewed studies showed that Panxs contribute to the transport of pain signaling via interfering with calcium and ATP homeostasis. Moreover, Panxs commence the inflammation process by elevation of the inflammatory cytokine production from immune cells. Recent evidence has suggested the key role of Panx channels in external dentin stimulation-induced ATP liberation.
Keywords: Pannexin channels, Oral health, Inflammation, Dentin, Pulp, Periodontal tissue.
Introduction
Several stimuli can cause dentinal hypersensitivity or inflammatory tooth pain. The dentin structure and the function of the intra-dental nerves are influenced in dentinal hypersensitivity and if left untreated it can turn into a chronic inflammation in dentin, pulp, and periodontal tissues. The application of desensitizing agents could target the nerve function as well as the dentin-pulp complex. The current treatment strategies either impede pain signal conduction through the pulp nerve via induction of ion saturation in saliva or block dental tubules by means of arginine or hydroxyl appetites. However, these approaches cannot prevent inflammation totally. Thus, in order to find a definitive treatment option, the anatomic, physiologic and molecular factors in the induction of hypersensitivity have been investigated. Among several proposed mechanisms, the function of ATP as an extracellular neurotransmitter in the transmission of nociceptive electrical stimuli has been an interesting research field. ATP signaling has been deemed to have a critical role in dental pain and hypersensitivity. Pannexins (Panx) as the second family of GJ proteins have generated ATP-permeable channels in human dental pulps which are sensitive to mechanical stimuli. Pnx1, Pnx2, and Panx3 are three members of Panx family. Panxs contribute to the transport of pain signaling via interfering with calcium and ATP homeostasis. Moreover, Panxs commence the inflammation process by elevation of the inflammatory cytokine production from immune cells. Recent evidence has suggested the key role of Panx channels in external dentin stimulation-induced ATP liberation [1]. Inhibition of Panx channels has been concurrent with the reduction of pain in neuropathic diseases with promising effects. Panxs have been detected in the oral cavity mainly in fibroblast and epithelial cells [2]. Also, gingival soft tissues and odontoblasts have been found to express Panx in vivo and in vitro. This gives the idea that blocking Panx can be a novel therapeutic opportunity in acute chronic pain and inflammation-related diseases in the oral cavity. While Panx1 channel blocker, probenecid, has been implemented in the treatment of hyperuricemia, no study has yet applied it in oral diseases [3].
Pannexin channels in oral health
The surrounding stratified epithelium in the oral cavity contains clusters of islands called taste buds. Taste buds are located in the superior surface of the tongue, on the palate and epiglottis [4]. The concept of a tongue map determines different zones for the five tastes [5]. Taste buds have three major cell types with different tastes capability and functions. The most abundant cells are type I cells which express glutamate transporter that uptakes glutamate and taste salty senses. Also, a plasma membrane-bound nucleotide (NTPDase2) which hydrolyzes ATP has expressed in type I cells [6]. Glutamate and ATP serve as prominent neurotransmitters in taste buds. Type II cells or receptors cells are G protein-coupled receptors that bind bitter, umami and sweet compounds. Finally, type III or presynaptic cells generate synaptic junctions with nerve terminals and bind to sour compounds. Junctional proteins have an important role in the release of neurotransmitters from taste bud cells. ATP is liberated through Panx channels form the receptor cells while presynaptic cells secret serotonin or norepinephrine by calcium-dependent exocytosis [7]. When a gustatory stimulus excites taste buds, ATP secretion is commenced in receptor cells through activation of Panx channels which subsequently stimulates afferent nerve fibers. The second target of ATP is the adjacent presynaptic cells which will induce the release of serotonergic amines. Also, this secreted ATP acts as an autocrine transmitter via enhancing its own liberation through a positive feedback system [8]. This occurs via the excitation of ATP receptors P2X and P2Y on taste bud cells and sensory nerve fibers. On the other hand, serotonin exhibits negative feedback onto receptor cells which collectively shape the signal transmissions to the brains. Figure 1 illustrates the crucial role of Panx in taste buds.
Figure 1. The functional role of Pannexin channels in taste buds cells. Activation of receptor cells leads to the release of ATP through pannexin 1 channels which then excites ATP receptors (P2X, P2Y) both on taste cells and their sensory nerve fibers. Serotonin (5-HT) which is released from presynaptic cells blocks receptor cells.
Pannexin channels in dentin, pulp, and periodontal tissues
Dentin matrix proteins are secreted via odontoblasts during physiological and pathological processes. Different thermal, osmotic, chemical and mechanical stimuli induce reactionary dentin formation in enamel lesions. Moreover, the hydrodynamic and the velocity if dentinal fluid movements are increased in the dental tubules subsequent to the exposure of the dentine surface to various stimuli [9], which in turn results in the deformation of the cellular membrane in odontoblasts [10]. This deformation activates several mechano-sensitive transient receptor potential (TRP) channels located on the surface of odontoblasts [11]. The extracellular ATP released from damaged dental pulp tissue is received by functional G-protein and phospholipase C coupled nucleotide receptors in odontoblasts [10]. As mentioned before in response to the presence of mechano-sensitive-TRP channels ATP is released via Panx-1 channels. In fact, Panx 1 channels mediate dental pain transduction via the establishment of intercellular communications between odontoblasts and sensory neurons. Also, the presence of P2Y1 and P2Y2 receptors on the surface of odontoblasts facilitate the communication of these cells with each other [11]. It has been shown that Panx 1 channel inhibitor decreases the calcium surge in response to mechanical stimulation in nearby odontoblasts [10].
Conclusion
The latest reports on the role of pannexin channels in oral health especially in chronic inflammation in dentin, pulp, and periodontal tissues were highlighted in this paper. The reviewed literature showed that Panxs contribute to the transport of pain signaling via interfering with calcium and ATP homeostasis. Furthermore, Panxs commence the inflammation process by elevation of the inflammatory cytokine production from immune cells. Investigators have proposed the key role of Panx channels in external dentin stimulation-induced ATP liberation in recent years.
Conflict of interests
The authors declare that there are no conflicts of interest associated with this work.
References
HOW TO CITE
Eftekhari, A., Samiei, M., & Ahamadian, E. (2019). The role of pannexin channels in oral health. Journal of Advanced Chemical and Pharmaceutical Materials (JACPM), 2(1), 106-108. Retrieved from http://advchempharm.ir/journal/index.php/JACPM/article/view/81
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