The Non-neuronal Cholinergic System in the Endothelium: Evidence and Possible Pathobiologiacal Significance

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概要

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• An increasing body of knowledge indicates that the cholinergic system is not confined to the nervous system, but is practically ubiquitous. The present paper will address the question of the non-neuronal cholinergic system in vascular endothelial cells (EC). In tissue sections of human skin, immunohistochemical studies using confocal laser scanning microscopy showed ChAT (choline acetyltransferase) activity in the EC of dermal blood vessels. Positive ChAT immunoreactivity was also demonstrated in monolayer cultures of human umbilical vein EC (HUVEC) and a human angiosarcoma EC line (HAEND). That the synthesizing enzyme is not only present in EC, but also active was shown by measuring ChAT activity. Thus, in HUVEC cultures, ChAT activity amounted to 0.78 ± 0.15 nmol · mg protein− 1 · h− 1 (n = 3), but was only partially (about 50%) inhibited by the ChAT inhibitor bromoacetylcholine (30 μM). In HPLC measurements, a concentration of 22 ± 2 pmol acetylcholine (ACh) per 106 cells was found (n = 6). However, using a cholinesterase-packed analytical column to check the identity of the acetylcholine peak, the peak height was found to be reduced, although a significant peak still remained, indicating the existence of a compound closely related to ACh. Further immunocytochemical experiments indicated that EC in vitro also express the vesicular acetylcholine transporter (VAChT) system. Preliminary immunoelectron microscopic studies suggest a topographical association of VAChT with endothelial endocytotic vesicles. The presented experiments clearly demonstrate the existence of essential elements of the cholinergic system (ChAT, VAChT, ACh) in the human endothelium. The biological functions of ACh synthesized by endothelial cells are the focus of ongoing research activity.

• 社団法人 日本薬理学会の論文
• 2001-01-01

著者

• Bittinger Fernando

  Institute of Pathology, the Technical University (RWTH) of Aachen

• Kirkpatrick Charles

  Department Of Pathology University Of Mainz

• KIRKPATRICK C.

  Institute of Pathology, Johannes Gutenberg University

• UNGER Ron

  Institute of Pathology, Johannes Gutenberg University

• KRIEGSMANN Jorg

  Institute of Pathology, Johannes Gutenberg University

• KILBINGER Heinz

  Institute of Pharmacology, Johannes Gutenberg University

• WESSLER Ignaz

  Institute of Pharmacology, Johannes Gutenberg University

• KILBINGER Heinz

  Department of Pharmacology, University of Mainz

• BITTINGER Fernando

  Department of Pathology, University of Mainz

• Bittinger Fernando

  Department Of Pathology University Of Mainz

• Bittinger Fernando

  Institute Of Pathology Johannes Gutenberg University Mainz

• Kirkpatrick C.

  Institute Of Pathology Johannes Gutenberg-university

• Unger Ron

  Institute Of Pathology Johannes Gutenberg University

• Kilbinger Heinz

  Department Of Pharmacology University Of Mainz

• Wessler Ignaz

  Department Of Pharmacology University Of Mainz

• Kriegsmann Jorg

  Institute Of Pathology Johannes Gutenberg University

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