The Ca++/calmodulin-dependent protein kinase II inhibitors KN62 and KN93, and their inactive analogues KN04 and KN92, inhibit nicotinic activation of tyrosine hydroxylase in bovine chromaffin cells.
The possible role of Ca++/calmodulin-dependent protein kinase II (CAM-K-II) in the nicotinic activation of tyrosine hydroxylase in intact cultured bovine adrenal chromaffin cells has been investigated. Over the concentration range 3-30 microM, KN62, a specific CAM-K-II inhibitor, inhibited basal tyrosine hydroxylase activity and the activity stimulated by nicotine or K+ depolarisation. KN04, a structural analogue of KN62 which does not inhibit CAM-K-II, produced an identical concentration-dependent inhibition of basal and nicotine-stimulated tyrosine hydroxylase activity. Another CAM-K-II inhibitor, KN93, also inhibited nicotine and K+ stimulation of tyrosine hydroxylase activity; however, an inactive analogue of KN93, KN92, mimicked these effect. The results suggest that the inhibition of nicotine- and K+-stimulated tyrosine hydroxylase activity by KN62 and KN93 is not due to their ability to inhibit CAM-K-II.
Marley
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PD
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Thomson
K A
KA
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000311:Adrenal Glands / Q000201:enzymology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D002417:Cattle; D002460:Cell Line; D002837:Chromaffin Granules / Q000201:enzymology*; D004789:Enzyme Activation; D007546:Isoquinolines / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000096926:Benzenesulfonamides
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001596:Benzylamines; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D007546:Isoquinolines; D009538:Nicotine; D010879:Piperazines; D013449:Sulfonamides; D014446:Tyrosine 3-Monooxygenase; C072105:KN 93; D000096926:Benzenesulfonamides; C063302:KN 62