Evidence that tolbutamide induces prolactin secretion by a mechanism which does not involve blocking ATP-sensitive...

Tolbutamide is an important member of the sulfonylureas, drugs which stimulate secretion of several hormones, including insulin and prolactin (PRL), through a mechanism postulated to involve blocking ATP-sensitive K+ channels. In the present study, we have evaluated the hypothesis relating the induced secretion to an effect on K+ channels by examining the effect of tolbutamide and the ATP-sensitive K+ channel-opener, diazoxide, on PRL secretion by acutely dispersed perifused adenohypophyseal cells from young adult male rats. Five-min perifusion of 0.1-50 microM tolbutamide induced a concentration-correlated secretion of PRL with a minimum effective concentration of 0.1 microM. Both basal and 50 microM tolbutamide-induced PRL secretion were significantly suppressed by 10 microM dopamine or 2 microM nifedipine, which block Ca2+ influx through L-type channels, but not by 100 microM diazoxide, indicating that tolbutamide induces PRL secretion by a mechanism involving Ca2+ influx through L-type Ca2+ channels which is not related to its ability to block ATP-sensitive K+ channels.