S-Space College of Dentistry/School of Dentistry (치과대학/치의학대학원) Dept. of Dental Science(치의과학과) Theses (Ph.D. / Sc.D._치의과학과)
The role of G-protein-coupled receptor induced Ca2+ signaling in salivary gland cells
타액선 G-protein-coupled receptor에 의한 세포내 칼슘신호의 역할
- 치의학대학원 치의과학과
- Issue Date
- 서울대학교 대학원
- Salivary glands; GPCR; Calcium; Aquaporin5; Lipid raft; Xerostomia; Desipramine; Bradykinin
- 학위논문 (박사)-- 서울대학교 대학원 : 치의과학과 신경생물학 전공, 2016. 2. 최세영.
- Salivation is an important function of the salivary gland. The cells of salivary gland are non-excitable cells which lack the expression of voltage-sensitive channel but express G-protein coupled receptor (GPCR) which receives external signals and conducts physiological functions. In salivary gland, the function of GPCR is crucial for salivation. Therefore, a change in the signal transduction conducted by GPCR is thought to cause changes in salivation. The excretion of saliva from salivary gland is well known to be controlled by different external factors including neural input
however, not much research has been done on identifying the different types of GPCR that are involved in transferring these external signals. Also, the effect of different pharmaceutical drugs that cause xerostomia on the function of GPCR is not well established. Therefore, doing a research on identifying the role of GPCR signal transduction in salivary gland cell withholds a great significance and it has the potential to improve the field of exocrine physiology and clinical dentistry. By observing the effect of lipid raft disruption in three form of membrane events involved in muscarinic transcellular water movement, I attempted to understand the contribution of lipid raft in each steps of water movement. Thus, it was focused on identifying the correlation between the underlying mechanism of salivation and antidepressant. Especially, the results were revealed the involvement of the signal transduction conducted by GPCR with salivation. Furthermore, I revealed many different receptors, ion channels and membrane transporters that are yet undiscovered and understand the external signal transmission mechanism to identify the connection between the salivation and GPCR signal transduction pathway. First, I examined for changes in physiology functions of the GPCR in salivary gland cells by disruption of the lipid raft which is known to play an important role in membrane physiology. In this study, through the depletion of cholesterol, I can explain that MβCD effects on the salivary GPCR. Next, I treated desipramine in the salivary gland cells and confirmed mechanisms accordingly. Desipramine is known to cause dry mouth when taken long term. However, because not yet clarified for its mechanism, my results can be explained due to dry mouth caused desipramine. Finally, I found new GPCR in the human salivary gland cells. I was confirmed the expression of the bradykinin receptor, and my results suggested the role of bradykinin in human salivary gland cells.
Taken together, through this paper, the relationship between the lipid raft depletion and GPCR signaling were identified. And I described the mechanism of dry mouth caused by desipramine in salivary gland cells. Also I demonstrated the role of bradykinin in human salivary gland cells. So, I suggested that it is important to study the function of the salivary GPCR-induced calcium signals.