A newly recognized action of cholecystokinin on pancreatic acini-release of lactate dehydrogenase.
In the course of examining the actions of the cholecystokinin octapeptide (CCK-8) on pancreatic acini we found that CCK-8 can stimulate release of the large-molecular-weight cytoplasmic protein, lactate dehydrogenase (LDH) by as much as 6-fold. CCK-8-stimulated LDH release is mediated by a CCK-preferring receptor, detectable at 100 pM CCK-8, maximal at 100 nM CCK-8, constant for up to 30 min, reversible, not desensitized, and dependent on oxidative metabolism and incubation temperature but not on calcium in the extracellular medium. This action of CCK-8 is blocked by inhibitors of protein kinases, staurosporine, H-7, H-8 and H-9, but not by calmodulin antagonists, chlorpromazine, trifluoperazine or W-7. This action of CCK-8 on LDH release is not reproduced by TPA, 8Br-cAMP or A23187. Thus, it appears to be mediated by a previously uncharacterized protein kinase or an isoform of protein kinase C that is not maximally stimulated by TPA.
Digestive Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
S T
ST
Bhat
R
R
Vinayek
R T
RT
Jensen
J D
JD
Gardner
D000470:Alkaloids / Q000494:pharmacology; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019311:Staurosporine; D013696:Temperature; D013997:Time Factors
D000470:Alkaloids; D000621:Aminoisobutyric Acids; D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; C100049:2-aminoisobutyric acid; C058121:L 365260; D003847:Deoxyglucose; D007770:L-Lactate Dehydrogenase; D011494:Protein Kinases; D019311:Staurosporine; D020109:Devazepide; D012844:Sincalide