31 Calmodulin and calmodulin-dependent protein kinase II inhibit hormone secretion in human parathyroid adenoma Ming Lu1,2,3, Erik Berglund1, Catharina Larsson1,3, Anders Ho¨o¨g4, Lars-Ove Farnebo1 and Robert Bra¨nstro¨m1 1Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital L1:03, SE-171 76 Stockholm, Sweden 2Department of Geriatric Endocrinology, First Affiliated Hospital of Guangxi Medical University, NanNing, People’s Republic of China 3Center for Molecular Medicine (CMM), Karolinska University Hospital, SE-171 76 Stockholm, Sweden 4Department of Oncology–Pathology, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden (Correspondence should be addressed to M Lu at Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital; Email:
[email protected]) Abstract 2C 2C Intracellular calcium ([Ca ]i) is the most relevant modulator adenoma cells in spite of increased [Ca ]i. The inhibitory C of parathyroid hormone (PTH) secretion. Uniquely, an effect of Ca2 calmodulin on PTH secretion may be due to 2C increase in [Ca ]i results in an inhibition of PTH secretion, the absence of synaptotagmin 1 protein in parathyroid and it probably exerts its function via calcium-binding protein adenomas, as demonstrated by western blot analysis. An pathways. The ubiquitous calcium-binding proteins, calmo- increased extracellular calcium level acutely lowered the dulin and calmodulin-dependent protein kinase II (CaMKII), amount of active phosphorylated CaMKII (pCaMKII) in have well-established roles in regulated exocytosis in neurons adenoma cells in vitro, indicating the physiological importance and neuroendocrine cells. However, their roles in parathyroid of this pathway. Moreover, a negative correlation between the cells and PTH secretion are still unclear.