Intracellular calcium in the pancreas. Part 1. Role in physiological regulation

Background. The pancreas is a unique organ combining both exocrine and endocrine functions, with intracellular Ca2+ ac­ting as a central secondary messenger that coordinates these proces­ses. Under physiological conditions, Ca2+ regulates digestive enzyme secretion by acinar cells, bicarbonate secretion by ductal cells, as well as the activity of stellate and immune cells that support tissue homeostasis. However, calcium signaling in pancreatic cells remains insufficiently explored, particularly in the context of its complex intercellular interactions. Clarifying these mechanisms is essential for a deeper understanding of secretory regulation, cellular energy supply, antioxidant protection, and adaptation to physiolo­gical stress. The purpose was to provide a comprehensive overview of current insights into the mechanisms of intracellular calcium signaling in pancreatic cells under physiological conditions, with a particular focus on the regulatory role of Ca2+ in secretion, meta­bolism, and intercellular communication across acinar, ductal, stellate, and immune cell populations. Materials and methods. Recent scientific publications from PubMed, Scopus, and Google Scholar on calcium signaling in pancreatic acinar, ductal, stellate, and immune cells were analyzed. Results. In normal physiology, calcium signals in acinar cells are triggered by activation of acetylcholine and cholecystokinin receptors, initiating Ca2+ release from the endoplasmic reticulum via IP3R and RyR. These signals present as oscillations that ensure controlled exocytosis of secretory granules. Mitochondria act as buffers, absorbing excess Ca2+ while simultaneously stimulating ATP synthesis required for calcium pumps. Ductal cells, through calcium channels (TRPV6, Orai1), regulate ion transport and bicarbonate secretion, crucial for maintaining intestinal pH. Stellate cells respond to calcium signals by modulating activity and synthesizing extracellular matrix components, preserving tissue architecture. Immune cells, via P2Y receptors and calcium channels, produce cytokines and respond to metabolic stimuli, maintaining immune surveillance within the pancreas. These findings highlight a high level of integration between organelles and cells, ensuring precise coordination of pancreatic functions. Conclusions. Intracellular calcium is a universal regulator of pancreatic cell activity. The coordinated interplay between cal­cium channels, pumps, receptors, and regulatory proteins underlies physiological secretion, tissue homeostasis, adaptation to load, and intercellular communication. Understanding these processes provides a foundation for future research in pancreatology and the development of new therapeutic strategies.