KN-62, a calcium/calmodulin-dependent protein kinase II inhibitor, inhibits high potassium-stimulated prolactin secretion and intracellular calcium increases in anterior pituitary cells.
In isolated rat anterior pituitary cells, KN-62 (10 microM), an isoquinoline sulfonamide inhibitor of calcium/calmodulin-dependent protein kinase II, inhibited high KCl(50 milliM)-stimulated prolactin secretion almost completely, with an IC50 of 95 nM KN-62 inhibited TRH-induced prolactin secretion less effectively. KN-04, a compound that is over 100-fold less active in inhibiting purified calcium/calmodulin-dependent protein kinase II, also inhibited high KCl-stimulated prolactin secretion with an IC50 of 500 nM. KN-62 and KN-04 (10 microM) both inhibited high KCl-stimulated increases in intracellular Ca2+ concentrations. We conclude that KN-62 and KN-04 inhibit activation of voltage-dependent calcium channels in anterior pituitary cells either directly or indirectly.
Cui
Z J
ZJ
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA.
Hidaka
H
H
Dannies
P S
PS
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D010879:Piperazines / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D013997:Time Factors
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010879:Piperazines; D013973:Thyrotropin-Releasing Hormone; C063302:KN 62; D011189:Potassium Chloride; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011388:Prolactin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D011188:Potassium; D002118:Calcium