Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine* / analogs & derivatives*
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Animals
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Calcium / metabolism*
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
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Cells, Cultured
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Enzyme Inhibitors / pharmacology*
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Female
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Isoquinolines / pharmacology*
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Kinetics
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Piperazines / pharmacology*
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Pituitary Gland, Anterior / drug effects
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Pituitary Gland, Anterior / physiology*
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Potassium / pharmacology*
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Potassium Chloride / pharmacology
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Prolactin / pharmacology*
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Rats
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Rats, Sprague-Dawley
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Thyrotropin-Releasing Hormone / pharmacology
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Time Factors
Substances
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Enzyme Inhibitors
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Isoquinolines
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Piperazines
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Thyrotropin-Releasing Hormone
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KN 62
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Potassium Chloride
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Prolactin
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Calcium-Calmodulin-Dependent Protein Kinases
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Potassium
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Calcium