Entry
Name
Oxytocin signaling pathway - Bos taurus (cow)
Description
Oxytocin (OT) is a nonapeptide synthesized by the magno-cellular neurons located in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus. It exerts a wide variety of central and peripheral effects. However, its best-known and most well-established roles are stimulation of uterine contractions during parturition and milk release during lactation. Oxytocin also influences cardiovascular regulation and various social behaviors. The actions of OT are all mediated by one type of OT receptor (OTR). This is a transmembrane receptor belonging to the G-protein-coupled receptor superfamily. The main signaling pathway is the Gq/PLC/Ins3 pathway, but the MAPK and the RhoA/Rho kinase pathways are also activated, contributing to increased prostaglandin production and direct contractile effect on myometrial cells. In the cardiovascular system, OTR is associated with the ANP-cGMP and NO-cGMP pathways, which reduce the force and rate of contraction and increase vasodilatation.
Class
Organismal Systems; Endocrine system
BRITE hierarchy
Pathway map
Ortholog table
Organism
Bos taurus (cow) [GN:
bta ]
Gene
280888 OXT; oxytocin-neurophysin 1 preproprotein [KO:K05243 ]
536654 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
101905399 LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1-like [KO:K04368 ] [EC:2.7.12.2 ]
512254 MEF2C; myocyte-specific enhancer factor 2C [KO:K04454 ]
786886 ELK1; ETS domain-containing protein Elk-1 [KO:K04375 ]
508029 TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977 ] [EC:3.6.1.13 ]
281883 KCNJ2; inward rectifier potassium channel 2 [KO:K04996 ]
538479 KCNJ12; ATP-sensitive inward rectifier potassium channel 12 [KO:K05005 ]
540740 KCNJ14; ATP-sensitive inward rectifier potassium channel 14 [KO:K05007 ]
287026 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858 ] [EC:3.1.4.11 ]
281985 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858 ] [EC:3.1.4.11 ]
515669 PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858 ] [EC:3.1.4.11 ]
508888 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858 ] [EC:3.1.4.11 ]
408015 CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850 ]
408013 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851 ]
509779 CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853 ]
100337204 CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857 ]
327703 CACNB1; voltage-dependent L-type calcium channel subunit beta-1 [KO:K04862 ]
327667 CACNB2; voltage-dependent L-type calcium channel subunit beta-2 [KO:K04863 ]
282160 CACNB3; voltage-dependent L-type calcium channel subunit beta-3 [KO:K04864 ]
282161 CACNB4; voltage-dependent L-type calcium channel subunit beta-4 [KO:K04865 ]
282608 CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 precursor [KO:K04858 ]
785909 CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859 ]
519644 CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 precursor [KO:K04860 ]
784075 CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861 ]
781184 CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866 ]
286800 CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867 ]
538496 CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868 ]
519331 CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869 ]
529382 CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870 ]
521616 CACNG6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871 ]
539969 CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872 ]
317697 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958 ]
281878 ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959 ]
281879 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960 ]
617412 CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183 ]
533527 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348 ] [EC:3.1.3.16 ]
790867 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348 ] [EC:3.1.3.16 ]
511224 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446 ]
530401 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
541127 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333 ]
788119 NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334 ]
512665 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
534107 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
282324 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200 ]
504219 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
511961 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform 1 [KO:K07200 ]
282162 CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515 ] [EC:2.7.11.17 ]
525416 CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515 ] [EC:2.7.11.17 ]
530719 CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515 ] [EC:2.7.11.17 ]
532713 CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515 ] [EC:2.7.11.17 ]
505964 MYL9; myosin regulatory light polypeptide 9 [KO:K12755 ]
282318 PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269 ] [EC:3.1.3.16 ]
516175 PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269 ] [EC:3.1.3.16 ]
538829 PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269 ] [EC:3.1.3.16 ]
538606 PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270 ]
107131237 PPP1R12B; protein phosphatase 1 regulatory subunit 12B isoform X1 [KO:K12329 ]
512431 PPP1R12C; protein phosphatase 1 regulatory subunit 12C isoform X1 [KO:K17457 ]
281793 GNAS; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632 ]
281790 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
281791 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
539521 GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630 ]
281792 GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534 ]
530001 PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289 ] [EC:2.7.1.153 ]
614838 PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X3 [KO:K21290 ]
515621 PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290 ]
526088 KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997 ]
520743 KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000 ]
614969 KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002 ]
539844 KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999 ]
513497 CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference
Authors
Devost D, Wrzal P, Zingg HH
Title
Oxytocin receptor signalling.
Journal
Reference
Authors
Viero C, Shibuya I, Kitamura N, Verkhratsky A, Fujihara H, Katoh A, Ueta Y, Zingg HH, Chvatal A, Sykova E, Dayanithi G
Title
REVIEW: Oxytocin: Crossing the bridge between basic science and pharmacotherapy.
Journal
Reference
Authors
Gutkowska J, Jankowski M
Title
Oxytocin revisited: its role in cardiovascular regulation.
Journal
Reference
Authors
Vrachnis N, Malamas FM, Sifakis S, Deligeoroglou E, Iliodromiti Z
Title
The oxytocin-oxytocin receptor system and its antagonists as tocolytic agents.
Journal
Reference
Authors
Tom N, Assinder SJ
Title
Oxytocin in health and disease.
Journal
Reference
Authors
Strakova Z, Copland JA, Lolait SJ, Soloff MS
Title
ERK2 mediates oxytocin-stimulated PGE2 synthesis.
Journal
Reference
Authors
Slater DM, Zervou S, Thornton S
Title
Prostaglandins and prostanoid receptors in human pregnancy and parturition.
Journal
J Soc Gynecol Investig 9:118-24 (2002)
Reference
Authors
Shmygol A, Gullam J, Blanks A, Thornton S
Title
Multiple mechanisms involved in oxytocin-induced modulation of myometrial contractility.
Journal
Reference
Authors
Tahara M, Morishige K, Sawada K, Ikebuchi Y, Kawagishi R, Tasaka K, Murata Y
Title
RhoA/Rho-kinase cascade is involved in oxytocin-induced rat uterine contraction.
Journal
Reference
Authors
Slattery MM, Morrison JJ
Title
Preterm delivery.
Journal
Reference
Authors
Pont JN, McArdle CA, Lopez Bernal A
Title
Oxytocin-stimulated NFAT transcriptional activation in human myometrial cells.
Journal
Reference
Authors
Gutkowska J, Jankowski M, Lambert C, Mukaddam-Daher S, Zingg HH, McCann SM
Title
Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors in the heart.
Journal
Reference
Authors
Antunes-Rodrigues J, de Castro M, Elias LL, Valenca MM, McCann SM
Title
Neuroendocrine control of body fluid metabolism.
Journal
Reference
Authors
Lee ES, Uhm KO, Lee YM, Kwon J, Park SH, Soo KH
Title
Oxytocin stimulates glucose uptake in skeletal muscle cells through the calcium-CaMKK-AMPK pathway.
Journal
Reference
Authors
Cassoni P, Sapino A, Fortunati N, Munaron L, Chini B, Bussolati G
Title
Oxytocin inhibits the proliferation of MDA-MB231 human breast-cancer cells via cyclic adenosine monophosphate and protein kinase A.
Journal
Reference
Authors
Busnelli M, Peverelli E, Mantovani G, Spada A, Chini B
Title
Deciphering the specific role of G(alphai/o) isoforms: functional selective oxytocin ligands and somatostatin SST5 receptor mutants.
Journal
Reference
Authors
Reversi A, Rimoldi V, Brambillasca S, Chini B
Title
Effects of cholesterol manipulation on the signaling of the human oxytocin receptor.
Journal
Reference
Authors
Salmina AB, Lopatina O, Ekimova MV, Mikhutkina SV, Higashida H
Title
CD38/cyclic ADP-ribose system: a new player for oxytocin secretion and regulation of social behaviour.
Journal
Reference
Authors
Higashida H, Yokoyama S, Kikuchi M, Munesue T
Title
CD38 and its role in oxytocin secretion and social behavior.
Journal
Reference
Authors
Lopatina O, Inzhutova A, Salmina AB, Higashida H
Title
The roles of oxytocin and CD38 in social or parental behaviors.
Journal
Reference
Authors
Guse AH
Title
Second messenger function and the structure-activity relationship of cyclic adenosine diphosphoribose (cADPR).
Journal
Related pathway
KO pathway
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