Dopamine and somatostatin inhibition of prolactin secretion from MMQ pituitary cells: role of adenosine triphosphate-sensitive potassium channels.
The sulfonylurea glibenclamide, which is known to block ATP-sensitive potassium channels, increases, in a dose-dependent manner, the release of PRL from MMQ pituitary cells. Glibenclamide does not reduce the dopaminergic inhibition of forskolin-stimulated PRL secretion; conversely it almost completely abolishes the inhibitory effect of somatostatin (SRIF) on this parameter. The sulfonylurea dose dependently increases basal [Ca++]i, without affecting the increase in [Ca++]i induced by high concentrations of extracellular potassium. Glibenclamide does not modify dopamine-induced [Ca++]i reduction, whereas it abolishes the inhibitory effect of SRIF on basal [Ca++]i. In the presence of diazoxide, an opener of ATP-sensitive potassium channels, which lowers basal [Ca++]i, dopamine still reduces [Ca++]i whereas SRIF does not induce a further decrease. Glibenclamide induces the depolarization of the cell membrane and prevents the SRIF-evoked hyperpolarization. The hyperpolarization of the cell membrane induced by dopamine is not modified by glibenclamide. Diazoxide induces a cell membrane hyperpolarization that is enhanced by dopamine but not by SRIF. Finally, glibenclamide does not affect basal and stimulated adenylate cyclase activity. In conclusion, our findings show that, in MMQ cells, glibenclamide stimulates PRL release, suggesting an involvement of ATP-sensitive potassium channels in the regulation of PRL secretion. The reversal by glibenclamide of the effects of SRIF on calcium homeostasis, membrane potential, and PRL release suggests that this type of potassium channel participates to the somatostatinergic inhibition of PRL secretion. Conversely, we found that glibenclamide does not modify the dopaminergic inhibition of PRL secretion and second messenger systems, suggesting that ATP-sensitive potassium channels may not be involved in the inhibitory effect of dopamine on PRL release.
Dipartimento di Scienza delle Comunicazioni Umane, II Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli, Italy.
O
O
Meucci
E
E
Landolfi
A
A
Scorziello
M
M
Grimaldi
C
C
Ventra
T
T
Florio
A
A
Avallone
G
G
Schettini
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003981:Diazoxide / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011388:Prolactin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology*
D015221:Potassium Channels; D013004:Somatostatin; D000255:Adenosine Triphosphate; D011388:Prolactin; D003981:Diazoxide; D011188:Potassium; D005905:Glyburide; D002118:Calcium; D004298:Dopamine