Prazosin Stimulates the Release of Hepatic Triacylglycerole Lipase Caused from Primary-culture Rat Hepatocytes

Nakamura, Tetsuya; Kerakawati, Rie; Morita, Tetsuo

doi:10.1248/jhs.56.462

Cited by 3 publications

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“…12) In this study, we investigated whether this prazosinstimulated HTGL release was due to a mechanism involving an increase in intracellular cAMP levels. We found that prazosin-stimulated HTGL release was markedly suppressed by the adenylate cyclase (AC) inhibitors 2′,5′-dideoxyadenosine (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In a previous study, we investigated the release of HTGL from rat hepatocytes after stimulation with prazosin. 12) It was considered that PLC activation played an important role in HTGL release. However, elucidating the involvement of other protein kinases is currently in progress.…”

Section: Discussionmentioning

confidence: 99%

“…11) We recently found that prazosin stimulated the release of hepatic triacylglyceride lipase (HTGL; EC 3.1.1.3) from primary cultured rat hepatocytes via the activation of phospholipase C (PLC). 12) In this previous study, the region downstream to PLC was suggested to be highly involved in the Ca 2+ / calmodulin-dependent protein kinase-II rather than protein kinase C. However, other interactions may also have been involved.…”

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confidence: 83%

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Adenosine 3′,5′-Cyclic Monophosphate Involvement in Hepatic Triacylglyceride Lipase Release from Prazosin-Stimulated Primary Cultured Rat Hepatocytes

Nakamura

Morita

2014

Biological & Pharmaceutical Bulletin

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We recently found that hepatic triglyceride lipase (HTGL) was released from primary cultured rat hepatocytes after treatment with prazosin, an antagonist of alpha-1 adrenoceptors. However, the details of prazosin-induced HTGL release remain uncertain. Here we investigated whether changes in cAMP levels in hepatocytes were related to HTGL release from prazosin-stimulated hepatocytes. When hepatocytes were treated with prazosin, cAMP levels during stimulated release of HTGL increased in a time-and dosedependent manner. Stimulated release of HTGL was suppressed by the adenylate cyclase inhibitors MDL-12,330A and 2′,5′-dideoxyadenosine. Further, cAMP-dependent protein kinase A (PKA) activity in prazosinstimulated hepatocytes also increased in a time-and dose-dependent manner. Moreover, prazosin-stimulated HTGL release was suppressed by the PKA inhibitors H-89 and KT5720. These results suggest that prazosinstimulated HTGL release from hepatocytes was due to cAMP production and partly due to subsequent PKA activation in hepatocytes.Key words prazosin; hepatic lipase; cAMP; protein kinase A; hepatocyteis a well-known antagonist of alpha-1 adrenoceptors, and it is used in pharmacotherapy for hypertension, prostatomegaly, 1,2) and pheochromocytoma. Its pharmacological effects result from inhibition of alpha-1 adrenoceptors of vascular smooth muscles and the sphincter muscle of the urethra.3,4) Prazosin also has other effects, including increasing high density lipoprotein (HDL) cholesterol levels in hypertensive patients after long-term administration, 5) improving posttraumatic stress disorder (PTSD) symptoms, 6) and inducing prostate cancer cell apoptosis.7) In addition, prazosin administration results in increased lipoprotein lipase (LPL) activity [8][9][10] and decreased 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity in serum. 11)We recently found that prazosin stimulated the release of hepatic triacylglyceride lipase (HTGL; EC 3.1.1.3) from primary cultured rat hepatocytes via the activation of phospholipase C (PLC).12) In this previous study, the region downstream to PLC was suggested to be highly involved in the Ca 2+ / calmodulin-dependent protein kinase-II rather than protein kinase C. However, other interactions may also have been involved.HTGL hydrolyzes triacylglycerides (TG) in HDL and intermediate density lipoproteins, and it is considered to play an important role in lipid metabolism. [13][14][15][16] However, effects of HTGL other than this remain to be investigated.HTGL is synthesized and secreted when it is partially glycosylated in hepatocytes.17) It is also anchored to the plasma membranes of endothelial cells by electrostatic binding with heparan sulfate proteoglycans.18) However, details regarding the regulation of HTGL release from hepatocytes remain uncertain.Thus, in this study, we investigated whether prazosinstimulated HTGL release from hepatocytes was due to a mechanism involving increased cAMP levels and a subsequent increase in protein kinase A (PKA) activity. MATERIALS AND METHOD...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 83%

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