Tetracaine stimulates extracellular Ca 2+-independent insulin release

Abstract

The effect of the local anesthetic, tetracaine, on 45Ca efflux, cytoplasmic Ca 2+ concentration [Ca 2+] i and insulin secretion in pancreatic B-cells was studied. At a physiological level of [Ca 2+] 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 Ca 2+, 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 Ca 2+. At high (22 mM) or low (2.8 mM) glucose, [Ca 2+] i was increased by tetracaine in a dose-dependent manner. Tetracaine (2 mM) also increased the 45Ca 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 Ca 2+. Finally, tetracaine increased 45Ca efflux from islets perifused in the presence of thapsigargin. In conclusion, our data indicate that tetracaine releases Ca 2+ from a thapsigargin-insensitive store in pancreatic B-cells. Under suitable experimental conditions, insulin release can be elicited by a [Ca 2+] o-independent pathway. The existence of a ryanodine-like Ca 2+ channel in pancreatic B-cells is proposed.