Tetracaine stimulates extracellular Ca2+-independent insulin release

The effect of the local anesthetic, tetracaine, on Ca-45 efflux, cytoplasmic Ca2+ concentration [Ca2+](i) and insulin secretion in pancreatic B-cells was studied. At a physiological level of [Ca2+](o), tetracaine (0.1-5 mM) dose-dependently inhibited insulin secretion induced by 22 mM glucose. Paradoxically, at the same glucose concentration but in the absence of external Ca2+, tetracaine dose-dependently increased insulin secretion. At a low glucose level (2.8 mM) tetracaine failed to affect secretion, either in the presence or absence of external Ca2+. At high (12 mM) or low (2.8 mM) glucose, [Ca2+](i) was increased by tetracaine in a dose-dependent manner. Tetracaine (2 mM) also increased the Ca-45 efflux from isolated islets. This effect was of the same magnitude at both low and high glucose concentrations, and was independent of the presence of extracellular Ca2+. Finally, tetracaine increased Ca-45 efflux from islets perifused in the presence of thapsigargin. In conclusion, our data indicate that tetracaine releases Ca2+ from a thapsigargin-insensitive store in pancreatic B-cells. Under suitable experimental conditions, insulin release can be elicited by a [Ca2+](o)-independent pathway. The existence of a ryanodine-like Ca2+ channel in pancreatic B-cells is proposed.