id: MODULE:endothelin_receptor_signaling
title: Endothelin receptor signaling pathway module
description: >-
The endothelin receptor signaling pathway (GO:0086100) and its canonical phospholipase
C-activating branch (GO:0160135) are initiated when the secreted 21-amino-acid bicyclic
peptide hormones endothelin-1 (EDN1, PANTHER:PTHR13874:SF10), endothelin-2 (EDN2,
PANTHER:PTHR13874:SF9), and endothelin-3 (EDN3, PANTHER:PTHR13874:SF11) bind and activate
their cognate seven-transmembrane G protein-coupled receptors EDNRA (ETA,
PANTHER:PTHR46099:SF2; selective for EDN1 and EDN2 over EDN3) and EDNRB (ETB,
PANTHER:PTHR46099:SF3; equipotent for EDN1, EDN2, and EDN3) at the plasma membrane of
vascular smooth-muscle cells, endothelial cells, neural crest derivatives, and renal/cardiac
tissues. Agonist-bound EDNRA and EDNRB couple primarily to heterotrimeric Gq/11 proteins
(exemplified by GNAQ, PANTHER:PTHR10218:SF329) to stimulate phospholipase C-beta (PLCB1,
PANTHER:PTHR10336:SF12), hydrolyzing phosphatidylinositol 4,5-bisphosphate (PIP2) into
inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) to mobilize intracellular Ca2+
and regulate vascular tone, systemic arterial blood pressure, and enteric/melanocytic neural
crest development.
status: DRAFT
evidence:
- source_id: GO:0086100
title: endothelin receptor signaling pathway
statement: >-
The module is grounded in the GO biological process term for the endothelin receptor
signaling pathway (GO:0086100) and its specific phospholipase C-activating branch
(GO:0160135).
- source_id: GO:0160135
title: phospholipase C-activating endothelin receptor signaling pathway
statement: >-
Models the canonical Gq/11-phospholipase C-activating endothelin receptor signaling
cascade (GO:0160135) triggered by EDN1, EDN2, and EDN3 across EDNRA and EDNRB.
- source_id: Reactome:R-HSA-388560
title: EDNRA,EDNRB bind EDNs
supporting_text: >-
There are 3 isoforms derived from the genes EDN1, EDN2 and EDN3 (Inoue et al. 1989).
EDNs
bind to two receptors (Elshourbagy et al. 1993), EDNRA (Adachi et al. 1991) and EDNRB
(Nakamuta et al. 1991).
statement: >-
Establishes that all three endothelin isopeptides (EDN1, EDN2, EDN3) bind and activate
the endothelin GPCRs EDNRA and EDNRB.
- source_id: PMID:2649896
title: 'The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes.'
supporting_text: >-
Moreover, each of the human genes predicted a putative 21-residue peptide, similar to but
distinct from each other: (i) the "classical" endothelin (ET-1), (ii) [Trp6,Leu7]endothelin
(ET-2), and (iii) [Thr2,Phe4,Thr5,Tyr6, Lys7,Tyr14]endothelin (ET-3). Synthetic ET-1,
ET-2, and ET-3 were prepared according to the deduced amino acid sequences, and the
biological activities were assayed by contraction of isolated porcine coronary artery strips
and by intravenous injection to anesthetized rats. All these synthetic peptides produced
strong vasoconstrictor and pressor responses.
statement: >-
Demonstrates that the three human genes EDN1, EDN2, and EDN3 encode distinct 21-residue
vasoactive endothelin peptide hormones.
- source_id: PMID:1917960
title: Effects of endothelins on signal transduction and proliferation in human melanocytes.
supporting_text: >-
Upon incubation with cultured cells, the mass contents of inositol 1,4,5-trisphosphate and
intracellular calcium level were substantially increased by 10 nM ET-1, ET-2, and ET-3, but
not by big-ET with maximal response at 80-130-s postincubation.
statement: >-
Establishes that mature ET-1 (EDN1), ET-2 (EDN2), and ET-3 (EDN3) directly stimulate
phospholipase C to generate IP3 and mobilize intracellular Ca2+ (GO:0160135).
- source_id: PMID:1713452
title: Cloning and functional expression of human cDNA for the ETB endothelin receptor.
supporting_text: >-
COS cells transiently transfected with the cloned cDNA expressed specific, high-affinity
binding sites for endothelin isopeptides and responded to the peptides with a transient
increase of [Ca2+]i; endothelin-1 and endothelin-3 exhibited approximately equal potencies
both in displacing 125I-labeled endothelin-1 binding and in eliciting [Ca2+]i transients.
statement: >-
Demonstrates that human EDNRB binds EDN1 and EDN3 with equal potency to trigger
intracellular Ca2+ mobilization.
- source_id: PANTHER:PTN000356323
title: PAINT node PTN000356323 for the endothelin family (PTHR13874)
statement: >-
Local PAINT IBD root node in PTHR13874 with propagated terms C:GO:0005576, F:GO:0005179,
F:GO:0031708, P:GO:0003100, P:GO:0006874, P:GO:0014826, P:GO:0045987; PAINT date 20260529.
notes: >-
Curated signaling-pathway module for the endothelin receptor signaling pathway (GO:0086100)
and its phospholipase C-activating branch (GO:0160135) built with PANTHER FAMILY/subfamily
selectors across the three endogenous endothelin peptide hormones EDN1 (PANTHER:PTHR13874:SF10),
EDN2 (PANTHER:PTHR13874:SF9), and EDN3 (PANTHER:PTHR13874:SF11), their cognate GPCRs EDNRA
(PANTHER:PTHR46099:SF2) and EDNRB (PANTHER:PTHR46099:SF3), and downstream Gq/11 alpha (GNAQ,
PANTHER:PTHR10218:SF329) and phospholipase C-beta (PLCB1, PANTHER:PTHR10336:SF12) effectors.
module:
id: endothelin_receptor_signaling
label: Endothelin receptor signaling pathway
module_type: SIGNALING_PATHWAY
concepts:
- preferred_term: endothelin receptor signaling pathway
term:
id: GO:0086100
label: endothelin receptor signaling pathway
description: >-
The series of molecular signals generated as a consequence of an endothelin receptor
(EDNRA or EDNRB) binding to one of its physiological endothelin peptide ligands (EDN1,
EDN2, or EDN3).
- preferred_term: phospholipase C-activating endothelin receptor signaling pathway
term:
id: GO:0160135
label: phospholipase C-activating endothelin receptor signaling pathway
description: >-
A phospholipase C-activating G protein-coupled receptor signaling pathway initiated by
endothelin binding to EDNRA or EDNRB and transduced via Gq/11 and phospholipase C-beta.
context:
taxa:
- preferred_term: Euteleostomi
term:
id: NCBITaxon:117571
label: Euteleostomi
cellular_components:
- preferred_term: extracellular region
term:
id: GO:0005576
label: extracellular region
- preferred_term: plasma membrane
term:
id: GO:0005886
label: plasma membrane
- preferred_term: cytosol
term:
id: GO:0005829
label: cytosol
parts:
- order: 1
role: endothelin peptide hormone ligand-receptor engagement
node:
id: endothelin_receptor_engagement
label: EDN1, EDN2, and EDN3 engagement of endothelin receptors EDNRA and EDNRB
module_type: REGULATORY_STEP
description: >-
Secreted mature 21-residue bicyclic endothelin peptides EDN1, EDN2, and EDN3 (generated
from big endothelins by endothelin-converting enzymes ECE1/ECE2) bind the orthosteric
pockets of the seven-transmembrane endothelin receptors EDNRA (ETA; selective for EDN1
and EDN2) and EDNRB (ETB; nonselective across EDN1, EDN2, and EDN3) at the plasma
membrane.
annotons:
- id: edn1_endothelin_1_ligand
label: EDN1 endothelin-1 peptide hormone ligand
participant:
selector_type: FAMILY
family:
preferred_term: Endothelin-1 subfamily
term:
id: PANTHER:PTHR13874:SF10
label: ENDOTHELIN-1
representative_members:
- preferred_term: EDN1
term:
id: UniProtKB:P05305
label: Endothelin-1
ancestral_nodes:
- preferred_term: PAINT node PTN000356323 for the endothelin family
term:
id: PANTHER:PTN000356323
label: PTN000356323
description: >-
Local PAINT IBD root node in PTHR13874 with propagated terms C:GO:0005576,
F:GO:0005179, F:GO:0031708, P:GO:0003100, P:GO:0006874, P:GO:0014826,
P:GO:0045987; PAINT date 20260529.
evidence:
- source_id: GO_REF:0000033
statement: IBD propagation from PAINT node PTN000356323 in PTHR13874.
evidence:
- source_id: file:interpro/panther/PTHR13874/PTHR13874-review.yaml
title: PTHR13874 PANTHER family review
statement: >-
PTHR13874 review confirms family-wide GO:0005179 (hormone activity) at
PTN000356323 and scopes GO:0086100 (endothelin receptor signaling pathway)
and GO:0160135 (phospholipase C-activating endothelin receptor signaling
pathway) to SF10 (EDN1), SF9 (EDN2), and SF11 (EDN3).
function:
preferred_term: hormone activity
term:
id: GO:0005179
label: hormone activity
processes:
- preferred_term: endothelin receptor signaling pathway
term:
id: GO:0086100
label: endothelin receptor signaling pathway
- preferred_term: phospholipase C-activating endothelin receptor signaling pathway
term:
id: GO:0160135
label: phospholipase C-activating endothelin receptor signaling pathway
locations:
- preferred_term: extracellular region
term:
id: GO:0005576
label: extracellular region
role_description: >-
Predominant vascular endothelial endothelin peptide hormone that binds and
activates both EDNRA and EDNRB with subnanomolar affinity to initiate
phospholipase C-activating endothelin receptor signaling.
evidence:
- source_id: Reactome:R-HSA-388560
title: EDNRA,EDNRB bind EDNs
supporting_text: >-
There are 3 isoforms derived from the genes EDN1, EDN2 and EDN3 (Inoue et al.
1989).
EDNs bind to two receptors (Elshourbagy et al. 1993), EDNRA (Adachi
et al. 1991) and EDNRB (Nakamuta et al. 1991).
statement: >-
Establishes EDN1 as a high-affinity endogenous agonist of both EDNRA and EDNRB.
- source_id: PMID:1917960
title: Effects of endothelins on signal transduction and proliferation in human melanocytes.
supporting_text: >-
Upon incubation with cultured cells, the mass contents of inositol
1,4,5-trisphosphate and intracellular calcium level were substantially
increased by 10 nM ET-1, ET-2, and ET-3, but not by big-ET
statement: >-
Demonstrates that mature EDN1 activates phospholipase C and IP3/Ca2+
signaling (GO:0160135).
- id: edn2_endothelin_2_ligand
label: EDN2 endothelin-2 peptide hormone ligand
participant:
selector_type: FAMILY
family:
preferred_term: Endothelin-2 subfamily
term:
id: PANTHER:PTHR13874:SF9
label: ENDOTHELIN-2
representative_members:
- preferred_term: EDN2
term:
id: UniProtKB:P20800
label: Endothelin-2
ancestral_nodes:
- preferred_term: PAINT node PTN000356323 for the endothelin family
term:
id: PANTHER:PTN000356323
label: PTN000356323
description: >-
Local PAINT IBD root node in PTHR13874 with propagated terms C:GO:0005576,
F:GO:0005179, F:GO:0031708, P:GO:0003100, P:GO:0006874, P:GO:0014826,
P:GO:0045987; PAINT date 20260529.
evidence:
- source_id: GO_REF:0000033
statement: IBD propagation from PAINT node PTN000356323 in PTHR13874.
evidence:
- source_id: file:interpro/panther/PTHR13874/PTHR13874-review.yaml
title: PTHR13874 PANTHER family review
statement: >-
PTHR13874 review confirms family-wide GO:0005179 (hormone activity) at
PTN000356323 and scopes GO:0086100 and GO:0160135 to SF10 (EDN1), SF9
(EDN2), and SF11 (EDN3).
function:
preferred_term: hormone activity
term:
id: GO:0005179
label: hormone activity
processes:
- preferred_term: endothelin receptor signaling pathway
term:
id: GO:0086100
label: endothelin receptor signaling pathway
- preferred_term: phospholipase C-activating endothelin receptor signaling pathway
term:
id: GO:0160135
label: phospholipase C-activating endothelin receptor signaling pathway
locations:
- preferred_term: extracellular region
term:
id: GO:0005576
label: extracellular region
role_description: >-
Endogenous endothelin isopeptide ([Trp6,Leu7]endothelin) that binds and activates
both EDNRA and EDNRB with high affinity to initiate phospholipase C-activating
endothelin receptor signaling.
evidence:
- source_id: Reactome:R-HSA-388560
title: EDNRA,EDNRB bind EDNs
supporting_text: >-
There are 3 isoforms derived from the genes EDN1, EDN2 and EDN3 (Inoue et al.
1989).
EDNs bind to two receptors (Elshourbagy et al. 1993), EDNRA (Adachi
et al. 1991) and EDNRB (Nakamuta et al. 1991).
statement: >-
Establishes EDN2 as a high-affinity endogenous agonist of both EDNRA and EDNRB.
- source_id: PMID:1917960
title: Effects of endothelins on signal transduction and proliferation in human melanocytes.
supporting_text: >-
Upon incubation with cultured cells, the mass contents of inositol
1,4,5-trisphosphate and intracellular calcium level were substantially
increased by 10 nM ET-1, ET-2, and ET-3, but not by big-ET
statement: >-
Demonstrates that mature EDN2 activates phospholipase C and IP3/Ca2+
signaling (GO:0160135).
- id: edn3_endothelin_3_ligand
label: EDN3 endothelin-3 peptide hormone ligand
participant:
selector_type: FAMILY
family:
preferred_term: Endothelin-3 subfamily
term:
id: PANTHER:PTHR13874:SF11
label: ENDOTHELIN-3
representative_members:
- preferred_term: EDN3
term:
id: UniProtKB:P14138
label: Endothelin-3
ancestral_nodes:
- preferred_term: PAINT node PTN000356323 for the endothelin family
term:
id: PANTHER:PTN000356323
label: PTN000356323
description: >-
Local PAINT IBD root node in PTHR13874 with propagated terms C:GO:0005576,
F:GO:0005179, F:GO:0031708, P:GO:0003100, P:GO:0006874, P:GO:0014826,
P:GO:0045987; PAINT date 20260529.
evidence:
- source_id: GO_REF:0000033
statement: IBD propagation from PAINT node PTN000356323 in PTHR13874.
evidence:
- source_id: file:interpro/panther/PTHR13874/PTHR13874-review.yaml
title: PTHR13874 PANTHER family review
statement: >-
PTHR13874 review confirms family-wide GO:0005179 (hormone activity) at
PTN000356323 and scopes GO:0086100 and GO:0160135 to SF10 (EDN1), SF9
(EDN2), and SF11 (EDN3).
function:
preferred_term: hormone activity
term:
id: GO:0005179
label: hormone activity
processes:
- preferred_term: endothelin receptor signaling pathway
term:
id: GO:0086100
label: endothelin receptor signaling pathway
- preferred_term: phospholipase C-activating endothelin receptor signaling pathway
term:
id: GO:0160135
label: phospholipase C-activating endothelin receptor signaling pathway
locations:
- preferred_term: extracellular region
term:
id: GO:0005576
label: extracellular region
role_description: >-
Endogenous endothelin isopeptide that binds and activates EDNRB with high affinity
(and EDNRA at higher concentrations) to initiate phospholipase C-activating
endothelin receptor signaling essential for enteric and melanocytic neural crest
development and vascular regulation.
evidence:
- source_id: PMID:1713452
title: Cloning and functional expression of human cDNA for the ETB endothelin receptor.
supporting_text: >-
endothelin-1 and endothelin-3 exhibited approximately equal potencies both in
displacing 125I-labeled endothelin-1 binding and in eliciting [Ca2+]i
transients.
statement: >-
Establishes EDN3 as a full, equipotent endogenous agonist of EDNRB eliciting
intracellular Ca2+ transients.
- source_id: PMID:1917960
title: Effects of endothelins on signal transduction and proliferation in human melanocytes.
supporting_text: >-
Upon incubation with cultured cells, the mass contents of inositol
1,4,5-trisphosphate and intracellular calcium level were substantially
increased by 10 nM ET-1, ET-2, and ET-3, but not by big-ET
statement: >-
Demonstrates that mature EDN3 directly stimulates phospholipase C and IP3/Ca2+
mobilization (GO:0160135).
- id: ednra_receptor
label: EDNRA endothelin-1 receptor (ETA)
participant:
selector_type: FAMILY
family:
preferred_term: Endothelin-1 receptor subfamily
term:
id: PANTHER:PTHR46099:SF2
label: ENDOTHELIN-1 RECEPTOR
representative_members:
- preferred_term: EDNRA
term:
id: UniProtKB:P25101
label: Endothelin-1 receptor
evidence:
- source_id: Reactome:R-HSA-388560
title: EDNRA,EDNRB bind EDNs
supporting_text: >-
EDNRA is primarily located in the smooth muscle of blood vessels. EDN binding
to EDNRA results in vasoconstriction and sodium retention, leading to
increased blood pressure.
statement: >-
Establishes EDNRA (ETA) as the vascular smooth-muscle endothelin GPCR.
function:
preferred_term: endothelin receptor activity
term:
id: GO:0004962
label: endothelin receptor activity
processes:
- preferred_term: endothelin receptor signaling pathway
term:
id: GO:0086100
label: endothelin receptor signaling pathway
- preferred_term: phospholipase C-activating endothelin receptor signaling pathway
term:
id: GO:0160135
label: phospholipase C-activating endothelin receptor signaling pathway
locations:
- preferred_term: plasma membrane
term:
id: GO:0005886
label: plasma membrane
role_description: >-
Seven-transmembrane G protein-coupled endothelin receptor type A (ETA) that binds
EDN1 and EDN2 with high affinity and activates heterotrimeric Gq/11-phospholipase
C signaling.
evidence:
- source_id: Reactome:R-HSA-388560
title: EDNRA,EDNRB bind EDNs
supporting_text: >-
EDNs bind to two receptors (Elshourbagy et al. 1993), EDNRA (Adachi et al. 1991)
and EDNRB (Nakamuta et al. 1991).
statement: >-
Establishes EDNRA as a principal mammalian endothelin receptor.
- id: ednrb_receptor
label: EDNRB endothelin receptor type B (ETB)
participant:
selector_type: FAMILY
family:
preferred_term: Endothelin receptor type B subfamily
term:
id: PANTHER:PTHR46099:SF3
label: ENDOTHELIN RECEPTOR TYPE B
representative_members:
- preferred_term: EDNRB
term:
id: UniProtKB:P24530
label: Endothelin receptor type B
evidence:
- source_id: PMID:1713452
title: Cloning and functional expression of human cDNA for the ETB endothelin receptor.
supporting_text: >-
endothelin-1 and endothelin-3 exhibited approximately equal potencies both
in displacing 125I-labeled endothelin-1 binding and in eliciting [Ca2+]i
transients.
statement: >-
Establishes EDNRB (ETB) as the nonselective endothelin GPCR activated
equipotently by EDN1, EDN2, and EDN3.
function:
preferred_term: endothelin receptor activity
term:
id: GO:0004962
label: endothelin receptor activity
processes:
- preferred_term: endothelin receptor signaling pathway
term:
id: GO:0086100
label: endothelin receptor signaling pathway
- preferred_term: phospholipase C-activating endothelin receptor signaling pathway
term:
id: GO:0160135
label: phospholipase C-activating endothelin receptor signaling pathway
locations:
- preferred_term: plasma membrane
term:
id: GO:0005886
label: plasma membrane
role_description: >-
Seven-transmembrane G protein-coupled endothelin receptor type B (ETB) that binds
EDN1, EDN2, and EDN3 with equal affinity and activates heterotrimeric
Gq/11-phospholipase C signaling.
evidence:
- source_id: PMID:1713452
title: Cloning and functional expression of human cDNA for the ETB endothelin receptor.
supporting_text: >-
COS cells transiently transfected with the cloned cDNA expressed specific,
high-affinity binding sites for endothelin isopeptides and responded to the
peptides with a transient increase of [Ca2+]i
statement: >-
Establishes EDNRB as a nonselective endothelin receptor coupled to Ca2+
mobilization.
- order: 2
role: Gq/11 and phospholipase C-beta effector activation
node:
id: endothelin_gq_plc_coupling
label: Gq/11 and phospholipase C-beta effector activation downstream of EDNRA/EDNRB
module_type: REGULATORY_STEP
description: >-
Agonist-activated EDNRA and EDNRB catalyze GDP-to-GTP exchange on heterotrimeric Gq/11
alpha subunits (exemplified by GNAQ), which directly stimulate plasma-membrane
phospholipase C-beta (exemplified by PLCB1) to hydrolyze PIP2 into IP3 and DAG and
mobilize intracellular Ca2+.
annotons:
- id: gnaq_gq_alpha
label: GNAQ Gq alpha subunit
participant:
selector_type: FAMILY
family:
preferred_term: Guanine nucleotide-binding protein G(q) subunit alpha subfamily
term:
id: PANTHER:PTHR10218:SF329
label: GUANINE NUCLEOTIDE-BINDING PROTEIN G(Q) SUBUNIT ALPHA
representative_members:
- preferred_term: GNAQ
term:
id: UniProtKB:P50148
label: Guanine nucleotide-binding protein G(q) subunit alpha
evidence:
- source_id: Reactome:R-HSA-416476
title: G alpha (q) signalling events
supporting_text: >-
The classic signalling route for G alpha (q) is activation of phospholipase
C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization
and protein kinase C activation.
statement: >-
Activated Gq/11 alpha subunits stimulate phospholipase C-beta to trigger
phosphoinositide hydrolysis and calcium mobilization.
function:
preferred_term: G protein activity
term:
id: GO:0003925
label: G protein activity
processes:
- preferred_term: endothelin receptor signaling pathway
term:
id: GO:0086100
label: endothelin receptor signaling pathway
- preferred_term: phospholipase C-activating endothelin receptor signaling pathway
term:
id: GO:0160135
label: phospholipase C-activating endothelin receptor signaling pathway
locations:
- preferred_term: plasma membrane
term:
id: GO:0005886
label: plasma membrane
role_description: >-
Heterotrimeric Gq alpha subunit activated by ligand-bound EDNRA and EDNRB to
stimulate phospholipase C-beta.
evidence:
- source_id: Reactome:R-HSA-416476
title: G alpha (q) signalling events
supporting_text: >-
The classic signalling route for G alpha (q) is activation of phospholipase C
beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and
protein kinase C activation.
statement: >-
Establishes that activated Gq/11 alpha subunits signal by stimulating
phospholipase C-beta.
- id: plcb1_phospholipase_c_beta
label: PLCB1 phospholipase C-beta-1 effector
participant:
selector_type: FAMILY
family:
preferred_term: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 subfamily
term:
id: PANTHER:PTHR10336:SF12
label: 1-PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE PHOSPHODIESTERASE BETA-1
representative_members:
- preferred_term: PLCB1
term:
id: UniProtKB:Q9NQ66
label: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1
evidence:
- source_id: PMID:1917960
title: Effects of endothelins on signal transduction and proliferation in human melanocytes.
supporting_text: >-
Upon incubation with cultured cells, the mass contents of inositol
1,4,5-trisphosphate and intracellular calcium level were substantially
increased by 10 nM ET-1, ET-2, and ET-3, but not by big-ET
statement: >-
Endothelin receptor activation stimulates phospholipase C-beta to generate
IP3 and mobilize intracellular Ca2+.
function:
preferred_term: phosphatidylinositol phospholipase C activity
term:
id: GO:0004435
label: phosphatidylinositol phospholipase C activity
processes:
- preferred_term: endothelin receptor signaling pathway
term:
id: GO:0086100
label: endothelin receptor signaling pathway
- preferred_term: phospholipase C-activating endothelin receptor signaling pathway
term:
id: GO:0160135
label: phospholipase C-activating endothelin receptor signaling pathway
locations:
- preferred_term: plasma membrane
term:
id: GO:0005886
label: plasma membrane
role_description: >-
Phospholipase C-beta effector activated by GTP-bound GNAQ downstream of EDNRA and
EDNRB to generate IP3 and DAG.
evidence:
- source_id: PMID:1917960
title: Effects of endothelins on signal transduction and proliferation in human melanocytes.
supporting_text: >-
Upon incubation with cultured cells, the mass contents of inositol
1,4,5-trisphosphate and intracellular calcium level were substantially
increased by 10 nM ET-1, ET-2, and ET-3, but not by big-ET
statement: >-
Demonstrates phospholipase C activation in endothelin receptor signaling.
connections:
- source: endothelin_receptor_engagement
target: endothelin_gq_plc_coupling
connection_type: CAUSES
description: >-
Binding of mature EDN1, EDN2, or EDN3 to EDNRA or EDNRB stabilizes the active receptor
conformation that catalyzes GDP-to-GTP exchange on GNAQ and activates PLCB1.