TETRACAINE STIMULATES EXTRACELLULAR CA2-INDEPENDENT INSULIN RELEASE()

The effect of the local anesthetic, tetracaine, on Ca-45 efflux, cytop lasmic Ca2+ concentration [Ca2+](i) and insulin secretion in pancreati c B-cells was studied. At a physiological level of [Ca2+](o), tetracai ne (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 i nsulin 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 t etracaine in a dose-dependent manner. Tetracaine (2 mM) also increased the Ca-45 efflux from isolated islets. This effect was of the same ma gnitude at both low and high glucose concentrations, and was independe nt of the presence of extracellular Ca2+. Finally, tetracaine increase d 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 e xperimental conditions, insulin release can be elicited by a [Ca2+](o) -independent pathway. The existence of a ryanodine-like Ca2+ channel i n pancreatic B-cells is proposed.