Temocapril prevents motor neuron damage and upregulation of cyclooxygenase-II in glutamate-induced neurotoxicity.
To examine the possible neuroprotective effect of temocapril, one kind of angiotensin-converting enzyme inhibitor, against glutamate-induced neurotoxicity, we analyzed the pharmacologic utility of temocapril in a post-natal organotypic culture model of motor neuron degeneration. Treatment with 10(-5) M of glutamate resulted in a motor neuron loss and decreased activity of choline acetyltransferase (ChAT). Cotreatment of 10(-5) M of glutamate and temocapril revealed protective effect on motor neuron death and decreased activity of ChAT. Next we performed reverse transcription-PCR analysis for cyclooxygenase-II (COX-II). COD-II mRNA was upregulated in glutamate-treated culture. Cotreatment with temocapril and glutamate inhibited upregulation of COX-II. Taken together, temocapril may have therapeutic potential for diseases which associate with upregulation of COX-II, in addition to its role in glutamate excitotoxicity.
Iwasaki
Yasuo
Y
Fourth Department of Internal Medicine, Toho University Ohashi Hospital, 2-17-6 Ohashi Meguro-ku, Tokyo 153-8515, Japan. yaso@med.toho-u.ac.jp
Ichikawa
Yasumitsu
Y
Igarashi
Osamu
O
Ikeda
Ken
K
Konno
Shingo
S
Aoyagi
Joe
J
Kinoshita
Masao
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2; D018698:Glutamic Acid / Q000633:toxicity; D007527:Isoenzymes / Q000187:drug effects* / Q000378:metabolism; D016472:Motor Neuron Disease / Q000139:chemically induced; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013841:Thiazepines / Q000494:pharmacology*; D015854:Up-Regulation
D000806:Angiotensin-Converting Enzyme Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D013841:Thiazepines; D018698:Glutamic Acid; C055603:temocapril hydrochloride; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D002795:Choline O-Acetyltransferase