Biomaterial Database

Molecular mechanism(s) of action of norepinephrine on the expression of the angiotensinogen gene in opossum kidney cells. 1998

T T Wang, and X H Wu, and S L Zhang, and J S Chan

Research Center, Maisonneuve-Rosemont Hospital, University of Montreal, Quebec, Canada.

BACKGROUND Norepinephrine (NE) is the major endogenous neurotransmitter of the renal sympathetic nerves interacting with both the alpha- and beta-adrenoceptors in the renal proximal tubules. We have previously reported that isoproterenol and iodoclonidine stimulate the expression of the angiotensinogen (ANG) gene in opossum kidney (OK) proximal tubular cells via the beta1-adrenoceptor and alpha2-adrenoceptor, respectively. We hypothesized that NE may interact with the beta- and/or alpha2-adrenoceptors to stimulate the expression of the ANG gene in OK cells. METHODS The fusion genes containing the various lengths of the 5'-flanking regulatory sequence of the rat ANG gene fused with a human growth hormone (hGH) gene as a reporter were stably transfected into the OK cells. The stimulatory effect of NE on the expression of the fusion genes was evaluated by the amount of immunoreactive hGH (IR-hGH) secreted into the culture medium. RESULTS The addition of NE stimulated the expression of the fusion gene, pOGH (ANG N-1498/+18) in a dose-dependent manner. The stimulatory effect of NE was inhibited in the presence of propranolol, atenolol, Rp-cAMP, yohimbine, staurosporine, H-7 and U73122 but not in the presence of ICI 118,551 and prazosin. The addition of a combination of isoproterenol and iodoclonidine synergistically stimulated the expression of pOGH (ANG N-1498/+18) as compared to the addition of isoproterenol and iodoclonidine alone. Furthermore, the addition of NE, forskolin, 8-Br-cAMP or phorbol 12-myristate (PMA) stimulated the expression of pOGH (ANG N-806/-779/-53/+18), a fusion gene containing the putative cAMP responsive element (CRE, ANG N-806/-779) upstream of the ANG promoter (ANG N-53/+ 18) in OK 95 cells, but had no effect on the expression of fusion genes containing the mutant of the CRE. CONCLUSIONS These studies demonstrate that the stimulatory effect of NE on the expression of the ANG gene in OK cells may be mediated via both the beta1- and alpha2-adrenoceptors and via the CRE (ANG N-806/-779) in the 5'flanking region of rat ANG gene.

UI	MeSH Term	Description	Entries
D007545	Isoproterenol	Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.	Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D009638	Norepinephrine	Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic.	Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D009893	Opossums	New World marsupials of the family Didelphidae. Opossums are omnivorous, largely nocturnal and arboreal MAMMALS, grow to about three feet in length, including the scaly prehensile tail, and have an abdominal pouch in which the young are carried at birth.	Didelphidae,Opossum
D011760	Pyrrolidinones	A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)	Pyrrolidinone,Pyrrolidone,Pyrrolidones
D004963	Estrenes	Unsaturated derivatives of the ESTRANES with methyl groups at carbon-13, with no carbon at carbon-10, and with no more than one carbon at carbon-17. They must contain one or more double bonds.	19-Norandrostenes,19 Norandrostenes
D005576	Colforsin	Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.	Coleonol,Forskolin,N,N-Dimethyl-beta-alanine-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho(2,1-b)pyran-6-yl Ester HCl,NKH 477,NKH-477,NKH477
D000808	Angiotensinogen	An alpha-globulin of about 453 amino acids, depending on the species. It is produced by the liver in response to lowered blood pressure and secreted into blood circulation. Angiotensinogen is the inactive precursor of the ANGIOTENSINS produced in the body by successive enzyme cleavages. Cleavage of angiotensinogen by RENIN yields the decapeptide ANGIOTENSIN I. Further cleavage of angiotensin I (by ANGIOTENSIN CONVERTING ENZYME) yields the potent vasoconstrictor octapeptide ANGIOTENSIN II; and then, via other enzymes, other angiotensins also involved in the hemodynamic-regulating RENIN-ANGIOTENSIN SYSTEM.	Hypertensinogen,Renin-Substrate,SERPINA8,Proangiotensin,Renin Substrate Tetradecapeptide,Serpin A8,Renin Substrate,Tetradecapeptide, Renin Substrate
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013755	Tetradecanoylphorbol Acetate	A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.	Phorbol Myristate Acetate,12-Myristoyl-13-acetylphorbol,12-O-Tetradecanoyl Phorbol 13-Acetate,Tetradecanoylphorbol Acetate, 4a alpha-Isomer,12 Myristoyl 13 acetylphorbol,12 O Tetradecanoyl Phorbol 13 Acetate,13-Acetate, 12-O-Tetradecanoyl Phorbol,Acetate, Phorbol Myristate,Acetate, Tetradecanoylphorbol,Myristate Acetate, Phorbol,Phorbol 13-Acetate, 12-O-Tetradecanoyl,Tetradecanoylphorbol Acetate, 4a alpha Isomer