Page last updated: 2024-10-24
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)
| Protein | Definition | Taxonomy |
|---|---|---|
| Type-1 angiotensin II receptor | An angiotensin II receptor 1 that is encoded in the genome of cow. [OMA:P25104, PRO:DNx] | Bos taurus (cattle) |
| Type-1 angiotensin II receptor | An angiotensin II receptor 1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P30556] | Homo sapiens (human) |
Compounds (46)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| 5-iodo-2-(oxaloamino)benzoic acid | organoiodine compound | ||
| candesartan | candesartan : 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 |
| thiorphan | Thiorphan: A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms. | N-acyl-amino acid | |
| avapro | irbesartan : 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 |
| losartan | losartan : 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 |
| propranolol | propranolol : 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 |
| atomoxetine | atomoxetine : 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 |
| ipsapirone | N-arylpiperazine | ||
| flesinoxan | |||
| valsartan | valsartan : 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 |
| tasosartan | tasosartan: angiotensin II antagonist; structure given in first source | biphenyls | |
| telmisartan | telmisartan : 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 117289 | GR 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 |
| exp3174 | losartan 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 692429 | L 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 antagonist | organic molecular entity | |
| exp7711 | EXP7711: to search, use E#P7711(nm); angiotensin II receptor antagonist; structure given in first source | ||
| bibs 39 | BIBS 39: structure given in first source; angiotensin II receptor antagonist | ||
| bibs 222 | BIBS 222: structure given in first source; angiotensin II receptor antagonist | ||
| forasartan | forasartan : 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 269-6 | UP 269-6: structure given in first source; angiotensin receptor antagonist | ||
| mk 996 | MK 996: an AT1-selective angiotensin II receptor antagonist; structure given in first source | ||
| bms 207940 | N-((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 ii | Giapreza: 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 |
| piboserod | Serotonin 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 158809 | L 158809: RN & structure given in first source; angiotensin receptor antagonist | ||
| 2-(oxaloamino)benzoic acid | (oxaloamino)benzoic acid | ||
| omapatrilat | omapatrilat: structure in first source | dipeptide | |
| caffeic acid | trans-caffeic acid : The trans-isomer of caffeic acid. | caffeic acid | geroprotector; mouse metabolite |
| cv 11194 | CV 11194: structure given in first source; an angiotensin II receptor antagonist | ||
| milfasartan | milfasartan: angiotensin I receptor antagonist; structure in first source | ||
| eprosartan | eprosartan : 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 123319 | PD123319 : 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 respectively | imidazopyridine | angiotensin receptor antagonist; endothelin receptor antagonist; vasoconstrictor agent |
| exp 655 | |||
| angiotensin ii, 1-sar-5-ile-8-ala- | |||
| saralasin | Saralasin: 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 162313 | L 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-nitrobenzoate | 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate: structure in first source | nitrobenzoic acid | |
| zd 7155 | |||
| bms 193884 | |||
| l 163491 | L 163491: structure given in first source | ||
| fimasartan | fimasartan: an angiotensin II receptor antagonist | biphenyls | |
| bms 248360 | |||
| ema401 | |||
| naluzotan | naluzotan: an antidepressant and anti-anxiety agent; structure in first source | ||
| nitd 609 | NITD 609: an antimalarial and coccidiostat; structure in first source |