title: Muscarinic acetylcholine receptor-mediated increase of angiotensin type 2 receptor mRNA in PC12 cells.
abstract: The present study examined changes in the angiotensin type 2 (AT2) receptor mRNA level after carbachol exposure in PC12 cells. The AT2 receptor mRNA level increased 2- to 3-fold after 12-18 h of carbachol exposure (100 microM). The up-regulation of AT2 receptor mRNA was antagonized by atropine, which is a muscarinic receptor antagonist, thus suggesting that the increase in AT2 receptor mRNA is mediated via muscarinic acetylcholine receptors. This increase is blocked by NG-nitro-L-arginine-methylester, nitric oxide (NO) synthase inhibitor, and hemoglobin NO trap. Protein kinase C (PKC) inhibitors, H-7 and calphostin C, inhibited the carbachol-induced upregulation. In addition, a G kinase inhibitor, ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), inhibited this increase. These findings suggest that the carbachol-induced increases in AT2 receptor mRNA is regulated by the activation of NO-cGMP and/or the PKC pathway.
authors.affiliation: Research Laboratory of Biodynamics, School of Medicine, Fukuoka University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shibata
authors.forename: M
authors.initials: M
authors.lastname: Ikuko
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Katsuragi
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D015870:Gene Expression; D018721:Muscarinic Agonists / Q000494:pharmacology; D016716:PC12 Cells; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000235:genetics*; D011976:Receptors, Muscarinic / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D018721:Muscarinic Agonists; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D011976:Receptors, Muscarinic; D002217:Carbachol