Evidence that tolbutamide induces prolactin secretion by a mechanism which does not involve blocking ATP-sensitive potassium channels.
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.
Wang
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Department of Medicine, Oregon Health Sciences University, Portland 97201.
Sato
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N
Greer
M A
MA
Greer
S E
SE
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003981:Diazoxide / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014044:Tolbutamide / Q000494:pharmacology*
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D011388:Prolactin; D014044:Tolbutamide; D009543:Nifedipine; D003981:Diazoxide; D004298:Dopamine