PT  - JOURNAL ARTICLE
AU  - T. J. Searl
AU  - E. M. Silinsky
TI  - Increases in Acetylcholine Release Produced by Phorbol Esters Are Not Mediated by Protein Kinase C at Motor Nerve Endings
DP  - 1998 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 247--251
VI  - 285
IP  - 1
4099  - http://jpet.aspetjournals.org/content/285/1/247.short
4100  - http://jpet.aspetjournals.org/content/285/1/247.full
SO  - J Pharmacol Exp Ther1998 Apr 01; 285
AB  - Recent work from our laboratory has demonstrated that phorbol esters known to stimulate protein kinase C (PKC) also stimulate acetylcholine (ACh) secretion by an action at a strategic component of the secretory apparatus [Redman et al. (1997)J Physiol (Lond) 501:41–48]. In an attempt to determine whether the stimulatory effects of phorbols are mediated by PKC, we examined the effects of several PKC antagonists on ACh release promoted by phorbol 12,13-dibutyrate (PDBu) at the frog neuromuscular junction. PKC antagonists that act at the ATP binding site (C3 domain) were examined for their ability to antagonize the stimulatory action of PDBu. Neither the nonselective PKC inhibitor, staurosporine (at concentrations as high as 1 μM), nor its more selective derivative, GF109203X (at concentrations as high as 10 μM), attenuated the stimulatory effects of PDBu. PKC antagonists that act at the phorbol ester binding site (C1 domain) were examined for their ability to antagonize the stimulatory action of PDBu. Neither sphingosine (500 μM) nor calphostin C (25 μM) reduced the stimulatory actions of PDBu on ACh release. These results suggest that a presynaptic protein possessing a phorbol ester receptor and not the enzyme PKC is the target site for the stimulatory effects of phorbol esters at motor nerve endings. The American Society for Pharmacology and Experimental Therapeutics