Increase in the intracellular Ca²⁺ concentration ( [Ca²⁺]_i ) in β-cells triggers insulin exocytosis. Among the Ca²⁺ channels, and receptors present in the plasma membrane, transient receptor potential (TRP) channels, and P2Y1 receptors are currently of great interest. The mechanism by which the extracellular Adenosine diphosphate ribose (ADPr) increases the [Ca²⁺]_i is unknown. Our aims were to study the involvement of TRP channels in tolbutamide induced [Ca²⁺]_i increase and to identify the surface receptor that is activated by ADPr.