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phospholipase C-activating angiotensin-activated signaling pathway

Definition

Target type: biologicalprocess

A phospholipase C-activating G protein-coupled receptor signaling pathway initiated by angiotensin binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:bf, GOC:BHF, GOC:mtg_cardiac_conduct_nov11]

The angiotensin-activated signaling pathway leading to phospholipase C activation is a complex cascade that plays a crucial role in regulating various cellular processes, including vasoconstriction, cell growth, and inflammation. The pathway is initiated by the binding of angiotensin II (Ang II) to its receptor, the angiotensin II type 1 receptor (AT1R), which is a G protein-coupled receptor (GPCR) located on the cell membrane. Upon Ang II binding, AT1R activates the heterotrimeric G protein, specifically the Gq subunit. Activated Gq protein then interacts with phospholipase C-beta (PLC-beta), a key enzyme in the pathway. PLC-beta hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2), a membrane phospholipid, into two signaling molecules: diacylglycerol (DAG) and inositol trisphosphate (IP3). DAG remains bound to the plasma membrane and activates protein kinase C (PKC), a family of serine/threonine kinases that phosphorylate various downstream targets, leading to diverse cellular responses. On the other hand, IP3 diffuses into the cytoplasm and binds to IP3 receptors located on the endoplasmic reticulum (ER) membrane. This binding triggers the release of calcium ions (Ca2+) from the ER into the cytosol, leading to a rapid increase in intracellular Ca2+ concentration. The rise in cytosolic Ca2+ concentration further activates PKC, enhances DAG production, and contributes to the activation of other Ca2+-dependent signaling pathways. The overall effect of the Ang II-activated signaling pathway is a complex interplay of signaling events that regulate various cellular functions. The pathway involves a cascade of events, including receptor activation, G protein activation, phospholipase C activation, and the production of second messengers, DAG and IP3, leading to downstream effects on PKC activation, calcium signaling, and ultimately, cellular responses.'
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Proteins (2)

ProteinDefinitionTaxonomy
Type-1 angiotensin II receptorAn angiotensin II receptor 1 that is encoded in the genome of cow. [OMA:P25104, PRO:DNx]Bos taurus (cattle)
Type-1 angiotensin II receptorAn angiotensin II receptor 1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P30556]Homo sapiens (human)

Compounds (46)

CompoundDefinitionClassesRoles
5-iodo-2-(oxaloamino)benzoic acidorganoiodine compound
candesartancandesartan : A benzimidazolecarboxylic acid that is 1H-benzimidazole-7-carboxylic acid substituted by an ethoxy group at position 2 and a ({2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl}methyl) group at position 1. It is a angiotensin receptor antagonist used for the treatment of hypertension.

candesartan: a nonpeptide angiotensin II receptor antagonist
benzimidazolecarboxylic acid;
biphenylyltetrazole
angiotensin receptor antagonist;
antihypertensive agent;
environmental contaminant;
xenobiotic
thiorphanThiorphan: A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms.N-acyl-amino acid
avaproirbesartan : A biphenylyltetrazole that is an angiotensin II receptor antagonist used mainly for the treatment of hypertension.

Irbesartan: A spiro compound, biphenyl and tetrazole derivative that acts as an angiotensin II type 1 receptor antagonist. It is used in the management of HYPERTENSION, and in the treatment of kidney disease.
azaspiro compound;
biphenylyltetrazole
angiotensin receptor antagonist;
antihypertensive agent;
environmental contaminant;
xenobiotic
losartanlosartan : A biphenylyltetrazole where a 1,1'-biphenyl group is attached at the 5-position and has an additional trisubstituted imidazol-1-ylmethyl group at the 4'-position

Losartan: An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.
biphenylyltetrazole;
imidazoles
angiotensin receptor antagonist;
anti-arrhythmia drug;
antihypertensive agent;
endothelin receptor antagonist
propranololpropranolol : A propanolamine that is propan-2-ol substituted by a propan-2-ylamino group at position 1 and a naphthalen-1-yloxy group at position 3.

Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.
naphthalenes;
propanolamine;
secondary amine
anti-arrhythmia drug;
antihypertensive agent;
anxiolytic drug;
beta-adrenergic antagonist;
environmental contaminant;
human blood serum metabolite;
vasodilator agent;
xenobiotic
atomoxetineatomoxetine : A secondary amino compound having methyl and 3-(2-methylphenoxy)-3-phenylpropan-1-yl substituents.aromatic ether;
secondary amino compound;
toluenes
adrenergic uptake inhibitor;
antidepressant;
environmental contaminant;
xenobiotic
ipsapironeN-arylpiperazine
flesinoxan
valsartanvalsartan : A monocarboxylic acid amide consisting of L-valine in which the amino hydrogens have been replaced by a pentanoyl and a [2'-(1H-tetrazol-5-yl)biphenyl]-4-yl]methyl group. It exhibits antihypertensive activity.

Valsartan: A tetrazole derivative and ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKER that is used to treat HYPERTENSION.
biphenylyltetrazole;
monocarboxylic acid;
monocarboxylic acid amide
angiotensin receptor antagonist;
antihypertensive agent;
environmental contaminant;
xenobiotic
tasosartantasosartan: angiotensin II antagonist; structure given in first sourcebiphenyls
telmisartantelmisartan : A member of the class of benzimidazoles used widely in the treatment of hypertension.

Telmisartan: A biphenyl compound and benzimidazole derivative that acts as an angiotensin II type 1 receptor antagonist. It is used in the management of HYPERTENSION.
benzimidazoles;
biphenyls;
carboxybiphenyl
angiotensin receptor antagonist;
antihypertensive agent;
EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor;
environmental contaminant;
xenobiotic
gr 117289GR 117289: angiotensin AT1 receptor antagonist; structure given in first source

zolasartan : A member of the class of 1-benzofurans that is 3-bromo-1-benzofuran which is substituted by a 2-(1H-tetrazol-5-yl)phenyl group at position 2 and by a (2-butyl-5-carboxy-4-chloro-1H-imidazol-1-yl)methyl group at position 5. It is an angiotensin II receptor type 1 (AT1) antagonist and was in clinical trials for the treatment of hypertension (now discontinued).
1-benzofurans;
biaryl;
imidazolyl carboxylic acid;
monocarboxylic acid;
organobromine compound;
organochlorine compound;
tetrazoles
angiotensin receptor antagonist;
antihypertensive agent
exp3174losartan carboxylic acid : A biphenylyltetrazole that is losartan with the hydroxymethyl group at position 5 on the imidazole ring replaced with a carboxylic acid.

losartan carboxylic acid: structure given in first source
biphenylyltetrazole;
imidazoles;
organochlorine compound
metabolite
l 692429L 692429: stimulates release of growth hormone; RN refers to (R)-isomer; structure given in first source
angiotensin ii, des-asp(1)-des-arg(2)-ile(5)-angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-: 3-8 hexapeptide fragment of angiotensin II; smallest potent angiotensin II antagonistorganic molecular entity
exp7711EXP7711: to search, use E#P7711(nm); angiotensin II receptor antagonist; structure given in first source
bibs 39BIBS 39: structure given in first source; angiotensin II receptor antagonist
bibs 222BIBS 222: structure given in first source; angiotensin II receptor antagonist
forasartanforasartan : A member of the class of pyridines that is pyridine which is substituted at positions 2 and 5 by o-(tetrazol-5-yl)phenyl and (3,5-dibutyl-1,2,4-triazol-1-yl)methyl groups, respectively. It is a nonpeptide antagonist of angiotensin II, type 1 (AT1) receptors, used for the treatment of hypertension.

forasartan: structure given in first source; an angiotensin AT(1) receptor antagonist; angiotensin II receptor antagonist; used in treatment of congestive heart failure
benzenes;
pyridines;
tetrazoles;
triazoles
angiotensin receptor antagonist;
antihypertensive agent
up 269-6UP 269-6: structure given in first source; angiotensin receptor antagonist
mk 996MK 996: an AT1-selective angiotensin II receptor antagonist; structure given in first source
bms 207940N-((2'-(((4,5-dimethyl-3-isoxazolyl)amino)sulfonyl)-4-(2-oxazolyl)(1,1'-biphenyl)-2-yl)methyl)-N,3,3-trimethylbutanamide: an ET(A) receptor antagonist; structure in first source
angiotensin iiGiapreza: injectable form of angiotensin II used to increase blood pressure in adult patients with septic or other distributive shock

Ile(5)-angiotensin II : An angiotensin II that acts on the central nervous system (PDB entry: 1N9V).
amino acid zwitterion;
angiotensin II
human metabolite
piboserodSerotonin 5-HT4 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT4 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN RECEPTOR AGONISTS.
l 158809L 158809: RN & structure given in first source; angiotensin receptor antagonist
2-(oxaloamino)benzoic acid(oxaloamino)benzoic acid
omapatrilatomapatrilat: structure in first sourcedipeptide
caffeic acidtrans-caffeic acid : The trans-isomer of caffeic acid.caffeic acidgeroprotector;
mouse metabolite
cv 11194CV 11194: structure given in first source; an angiotensin II receptor antagonist
milfasartanmilfasartan: angiotensin I receptor antagonist; structure in first source
eprosartaneprosartan : A member of the class of imidazoles and thiophenes that is an angiotensin II receptor antagonist used for the treatment of high blood pressure.

eprosartan: angiotensin II receptor antagonist
dicarboxylic acid;
imidazoles;
thiophenes
angiotensin receptor antagonist;
antihypertensive agent;
environmental contaminant;
xenobiotic
pd 123319PD123319 : An imidazopyridine consisting of 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine having 4-(dimethylamino)-3-methylbenzyl, diphenylacetyl and carboxy and groups at positions 1, 5 and 6 respectivelyimidazopyridineangiotensin receptor antagonist;
endothelin receptor antagonist;
vasoconstrictor agent
exp 655
angiotensin ii, 1-sar-5-ile-8-ala-
saralasinSaralasin: An octapeptide analog of angiotensin II (bovine) with amino acids 1 and 8 replaced with sarcosine and alanine, respectively. It is a highly specific competitive inhibitor of angiotensin II that is used in the diagnosis of HYPERTENSION.oligopeptide
l 162313L 162313: a biphenylimidazole derivative; a non-peptide angiotensin agonist; no further information available 2/95
4-oxo-6-((pyrimidin-2-ylthio)methyl)-4h-pyran-3-yl 4-nitrobenzoate4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate: structure in first sourcenitrobenzoic acid
zd 7155
bms 193884
l 163491L 163491: structure given in first source
fimasartanfimasartan: an angiotensin II receptor antagonistbiphenyls
bms 248360
ema401
naluzotannaluzotan: an antidepressant and anti-anxiety agent; structure in first source
nitd 609NITD 609: an antimalarial and coccidiostat; structure in first source