THE CA++ CALMODULIN-DEPENDENT PROTEIN-KINASE-II INHIBITORS KN62 AND KN93, AND THEIR INACTIVE ANALOGS 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 cu ltured bovine adrenal chromaffin cells has been investigated. Over the concentration range 3-30 mu M, KN62, a specific CAM-K-II inhibitor, i nhibited basal tyrosine hydroxylase activity and the activity stimulat ed by nicotine or K+ depolarisation. KN04, a structural analogue of KN 62 which does not inhibit CAM-K-II, produced an identical concentratio n-dependent inhibition of basal and nicotine-stimulated tyrosine hydro xylase activity. Another CAM-K-II inhibitor, KN93, also inhibited nico tine and K+ stimulation of tyrosine hydroxylase activity; however, an inactive analogue of KN93, KN92, mimicked these effect. The results su ggest that the inhibition of nicotine- and K+-stimulated tyrosine hydr oxylase activity by KN62 and KN93 is not due to their ability to inhib it CAM-K-II. (C) 1996 Academic Press, Inc.