Role of Protein kinase C in Desensitization of Somatostatin-induced Calcium Signalling in NG108-15 Cells.
10.3803/jkes.2005.20.4.353
- Author:
Kyoung Mi KIM
1
;
Jong Ho SUNG
;
Myung Jun KIM
;
Duck Joo RHIE
;
Yang Hyeok JO
;
Sang June HAHN
;
Myung Suk KIM
;
Shin Hee YOON
;
Bu Seung KIM
Author Information
1. Department of Internal Medicine and Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Somatostatin;
Desensitization;
Protein kinase C;
NG108-15 cells;
Ca2+;
Phospholipase C
- MeSH:
Calcium*;
Colforsin;
Down-Regulation;
Enkephalins;
GTP-Binding Proteins;
Inositol;
Protein Kinase C*;
Protein Kinases*;
Somatostatin;
Type C Phospholipases
- From:Journal of Korean Society of Endocrinology
2005;20(4):353-361
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Activation of G-protein coupled-somatostatin receptors induces the release of calcium from inositol 1, 4, 5-trisphosphate-sensitive intracelluar stores. G-protein-coupled receptor signaling decreases with prolonged exposure to an agonist. SEBJECTS and METHODS: Fura-2-based digital Ca2+ imaging was used to study the effects of prolonged exposure to an agonist on the somatostatin-induced intracellular Ca2+ concentration([Ca2+]i) increases in NG108-15 cells, which were differentiated with CO2-independent medium and 10micrometer forskolin. RESULTS: Exposure to somatostatin(1micrometer) for 30 min completely desensitized the NG108-15 cells to a second somatostatin-induced response. The cells recovered gradually over 20 min following washout of the somatostatin. The desensitization was not due to depletion of the intracellular Ca2+ stores, and pretreatment for 30 min with bradykinin(100nM), which activates phospholipase C, or DADLE(D-Ala2-D-Leu5 enkephalin, 1microM), which activates phospholipase C, failed to cross-desensitize the somatostatin-evoked [Ca2+]i increases. Treatment with 8-cpt-cAMP(0.1mM) for 30min did not influence the somatostatin-induced[Ca2+]i increases. Phorbol 12, 13-dibutyrate(PdBu, 1microM) blocked the response completely. Down-regulation of PKC due to 24 h exposure of PdBu (1microM) inhibited the somatostatin-induced desensitization. CONCLUSION: Prolonged exposure of somatostatin to NG108-15 cells desensitized the somatostatin-induced release of Ca2+ from the intracelluar store, with protein kinase C also involved in the desensitization.