Kinesin is involved in regulation of rat pancreatic amylase secretion

Background & Aims: Kinesin has recently been localized to zymogen granules of pancreatic acini and is suggested to participate in exocytosis of exocri ne pancreas, We examined the function of kinesin in regulated exocytosis of pancreatic acini in this study, Methods: Kinesin function in exocytosis wa s examined by introducing hexahistidine-tagged recombinant kinesin protein and antikinesin monoclonal antibody into streptolysin-O-permeabilized acini . Intracellular localization of introduced recombinant kinesin was investig ated by immunohistochemistry. Interaction between recombinant kinesin and t he microtubule network was confirmed by nocodazole pretreatment of acini, K inesin regulation by secretagogues was investigated by examining their effe ct on adenosine triphosphatase (ATPase) activity of endogenous kinesin, Res ults: Recombinant kinesin enhanced calcium-stimulated amylase release from streptolysin-O-permeabilized acini, Introduced recombinant kinesin was loca lized to both the microtubule network and zymogen granule, Nocodazole pretr eatment of acini abolished the enhancing effect of recombinant kinesin on c alcium-stimulated amylase release. Antikinesin antibody inhibited amylase r elease stimulated by the combination of calcium and cyclic adenosine monoph osphate (cAMP) but not that stimulated by calcium alone, Secretin and 8-bro mo-cAMP increased ATPase activity of endogenous kinesin. Conclusions: Kines in plays a stimulatory role in regulated exocytosis of pancreatic acini and is involved in stimulus-secretion coupling through a cAMP-dependent pathwa y.