Effects of Imidazoline Compounds on Cytoplasmic Ca²⁺ concentration and ATP-sensitive K+ channels in Pancreatic B-cells

Summary

Phentolamine, an α-adrenoceptor-blocking agent with an imidazoline structure, induces an increase in the cytoplasmic Ca²⁺ concentration of pancreatic B-cells. This effect occurs at a concentration (32 μM) at which phentolamine is able to enhance glucose-induced insulin secretion. The increase in cytoplasmic Ca²⁺ concentration caused by phentolamine is additive to the one elicited by a maximally effective concentration of tolbutamide (100 μM). Imidazoline-binding sites in insulin-secreting HIT cells can also be occupied by the guanidinium compound guanabenz which was found to be a potent and reversible blockers of ATP-dependent K⁺-channels in B-cells. In contrast to phentolamine, guanabenz blocks the ATP-dependent K⁺-channels only in the inside-out mode, but not in cell-attached mode of the patch-clamp technique In conclusion, imidazolines and structurally related compounds block ATP-dependent K⁺-channels b binding to the cytoplasmic face of the plasma membrane, and may have effects on other ion channel which contribute to the elevation of cytoplasmic Ca² concentration and, consequently, to insulin release.

Key words

Imidazolines - calcium - ion channels - insulin secretion - pancreatic islet