KEGG PATHWAY: map04921

PATHWAY: map04921

Entry

map04921                    Pathway

Name

Oxytocin signaling pathway

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

Pathway map

map04921

Oxytocin signaling pathway

Reference

PMID:18655881

Authors

Devost D, Wrzal P, Zingg HH

Title

Oxytocin receptor signalling.

Journal

Prog Brain Res 170:167-76 (2008)
DOI:10.1016/S0079-6123(08)00415-9

Reference

PMID:20626426

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

CNS Neurosci Ther 16:e138-56 (2010)
DOI:10.1111/j.1755-5949.2010.00185.x

Reference

PMID:21981277

Authors

Gutkowska J, Jankowski M

Title

Oxytocin revisited: its role in cardiovascular regulation.

Journal

J Neuroendocrinol 24:599-608 (2012)
DOI:10.1111/j.1365-2826.2011.02235.x

Reference

PMID:22190926

Authors

Vrachnis N, Malamas FM, Sifakis S, Deligeoroglou E, Iliodromiti Z

Title

The oxytocin-oxytocin receptor system and its antagonists as tocolytic agents.

Journal

Int J Endocrinol 2011:350546 (2011)
DOI:10.1155/2011/350546

Reference

PMID:19840865

Authors

Tom N, Assinder SJ

Title

Oxytocin in health and disease.

Journal

Int J Biochem Cell Biol 42:202-5 (2010)
DOI:10.1016/j.biocel.2009.10.008

Reference

PMID:9575824

Authors

Strakova Z, Copland JA, Lolait SJ, Soloff MS

Title

ERK2 mediates oxytocin-stimulated PGE2 synthesis.

Journal

Am J Physiol 274:E634-41 (1998)
DOI:10.1152/ajpendo.1998.274.4.E634

Reference

PMID:12009385

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

PMID:16787565

Authors

Shmygol A, Gullam J, Blanks A, Thornton S

Title

Multiple mechanisms involved in oxytocin-induced modulation of myometrial contractility.

Journal

Acta Pharmacol Sin 27:827-32 (2006)
DOI:10.1111/j.1745-7254.2006.00393.x

Reference

PMID:11861513

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

Endocrinology 143:920-9 (2002)
DOI:10.1210/endo.143.3.8696

Reference

PMID:12433531

Authors

Slattery MM, Morrison JJ

Title

Preterm delivery.

Journal

Lancet 360:1489-97 (2002)
DOI:10.1016/S0140-6736(02)11476-0

Reference

PMID:22902539

Authors

Pont JN, McArdle CA, Lopez Bernal A

Title

Oxytocin-stimulated NFAT transcriptional activation in human myometrial cells.

Journal

Mol Endocrinol 26:1743-56 (2012)
DOI:10.1210/me.2012-1057

Reference

PMID:9326674

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

Proc Natl Acad Sci U S A 94:11704-9 (1997)
DOI:10.1073/pnas.94.21.11704

Reference

PMID:14715914

Authors

Antunes-Rodrigues J, de Castro M, Elias LL, Valenca MM, McCann SM

Title

Neuroendocrine control of body fluid metabolism.

Journal

Physiol Rev 84:169-208 (2004)
DOI:10.1152/physrev.00017.2003

Reference

PMID:18555543

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

Regul Pept 151:71-4 (2008)
DOI:10.1016/j.regpep.2008.05.001

Reference

PMID:9219843

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

Int J Cancer 72:340-4 (1997)
DOI:10.1002/(SICI)1097-0215(19970717)72:2<340::AID-IJC23>3.0.CO;2-I

Reference

PMID:23356278

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

Biochem Soc Trans 41:166-71 (2013)
DOI:10.1042/BST20120306

Reference

PMID:16966388

Authors

Reversi A, Rimoldi V, Brambillasca S, Chini B

Title

Effects of cholesterol manipulation on the signaling of the human oxytocin receptor.

Journal

Am J Physiol Regul Integr Comp Physiol 291:R861-9 (2006)
DOI:10.1152/ajpregu.00333.2006

Reference

PMID:20141572

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

J Neuroendocrinol 22:380-92 (2010)
DOI:10.1111/j.1365-2826.2010.01970.x

Reference

PMID:22227279

Authors

Higashida H, Yokoyama S, Kikuchi M, Munesue T

Title

CD38 and its role in oxytocin secretion and social behavior.

Journal

Horm Behav 61:351-8 (2012)
DOI:10.1016/j.yhbeh.2011.12.011

Reference

PMID:23335873

Authors

Lopatina O, Inzhutova A, Salmina AB, Higashida H

Title

The roles of oxytocin and CD38 in social or parental behaviors.

Journal

Front Neurosci 6:182 (2012)
DOI:10.3389/fnins.2012.00182

Reference

PMID:16156781

Authors

Guse AH

Title

Second messenger function and the structure-activity relationship of cyclic adenosine diphosphoribose (cADPR).

Journal

FEBS J 272:4590-7 (2005)
DOI:10.1111/j.1742-4658.2005.04863.x

Related
pathway

map00590

Arachidonic acid metabolism

map04010

MAPK signaling pathway

map04020

Calcium signaling pathway

map04110

Cell cycle

KO pathway

ko04921

All links

Chemical substance (12)   
   KEGG COMPOUND (12)   
Gene (539674)   
   KEGG ORTHOLOGY (112)   
   RefGene (539562)   
Literature (21)   
   PubMed (21)   
All databases (539707)   

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