Two distinct XXXX -sensitive and -insensitive PKC up- and down-regulate an alpha-bungarotoxin-resistant nAChR1 in insect neurosecretory cells (DUM neurons).

@entity2366 @entity12703 @entity1239 @entity564 @entity668 @entity4515 @entity4621 @entity11039 @entity460 @entity4140 @entity141 @entity1140 @entity13231 @entity934
While there is mounting knowledge about the structure and diversity of insect neuronal nicotinic @entity934 receptors, less attention has been directed towards their intracellular regulation by @entity460 -mediated activation or inhibition of protein phosphorylation. The main goal of this work was to delineate the chain of molecular events that lead to the up- and down-regulation by two protein kinase Cs of an insect neuronal alpha-bungarotoxin-resistant nicotinic @entity934 receptor (called nAChR1). The native nicotinic @entity934 receptor intracellular regulation was studied on dissociated adult dorsal unpaired median neurons isolated from the terminal abdominal ganglion of the cockroach @entity564 using whole-cell patch-clamp technique and @entity460 imaging. We report that under 0.5 micro malpha-bungarotoxin treatment, the inward current produced by pressure ejection application of @entity1239 onto the cell body was differentially sensitive to specific protein kinase C activators and inhibitors. The @entity4621 PMA produced a @entity460 -dependent increase in current amplitude blocked by @entity668 . By contrast, the @entity2366 analogue @entity13231 produced a @entity460 -independent reduction of the nicotinic response, reversed by @entity12703 and @entity668 . This indicated that two protein kinase C isozymes ('classical' and 'novel' protein kinase C, named PKC1 and PKC2, respectively) up- and down-regulated nicotinic @entity934 receptor function. @entity4515 and @entity13231 effects were mimicked by @entity4140 -sensitive M1 muscarinic receptor subtype coupled to phospholipase C second messenger pathway. Low concentration of muscarine elevated internal @entity460 levels, which thereby activated PKC1. By contrast, a high concentration of @entity11039 strongly increased [ @entity141 ]i, which induced inhibition of PKC1. This effect was reversed by @entity1140 , suggesting the implication of PP2B which unmasked PKC2 activity mediating down-regulation of nicotinic @entity934 receptor.
