Dual action of the neuropeptide galanin on the cytoplasmic free calcium concentration in RIN m5F cells.

The neuropeptide, galanin, potently inhibits insulin secretion and is thought to be an adrenergic neurotransmitter in the pancreas. In this study, the effects of galanin and the galanin receptor antagonist, galantide, on the cytoplasmic free Ca2+ [Ca2+]i, were investigated in FURA 2-AM-loaded cells of the rat insulinoma cell line, RIN m5F, in cell suspensions in a cuvette. It was found that galanin (100 nmol/l) after a prior addition of D-glyceraldehyde (15 mmol/l), both at 3.3 and 8.3 mmol/l glucose, induced a dual, biphasic, action on the [Ca2+]i: a rapid and transient peak was followed by a reduction below the prestimulatory levels. The rapid peak was similar to that induced by the cholinergic agonist, carbachol (100 mumol/l). A prior addition of the galanin receptor antagonist, galantide (500 nmol/l), abolished the changes in [Ca2+]i after galanin. However, galantide by itself induced the same biphasic changes in [Ca2+]i as those induced by galanin. Hence, the study demonstrates a) that galanin induces a dual response in [Ca2+]i in insulin-producing RIN m5F cells with a rapid peak preceeding a reduction below prestimulatory levels, and b) that the galanin receptor antagonist, galantide, is a partial galanin agonist. It is proposed that the changes in [Ca2+]i induced by galanin are much more complex than previously thought and, therefore, that galanin does not inhibit insulin secretion by simply reducing the [Ca2+]i.