File:Oxytocin receptor pathways.jpg

The major mechanism is mediated by the Gq/PLC/InsP3 pathway. When oxytocin binds to OTR, it activates Gαq/11 and then phospholipase C (PLC), which induces the cleavage of PIP2 to inositoltrisphosphate (InsP3) and diacylglycerol (DAG).

InsP3 induces Ca2+ release from Ca2+ stores via InsP3R and, in some cells, causes Ca2+-induced Ca2+ release (CICR) via the ryanodine receptor (RyR). The activation of Gq also causes membrane depolarization*, which, in turn, activates VGCCs and then facilitates Ca2+ entry through VGCCs. Thus, increased cytosolic Ca2+ ([Ca2+]i) stimulates CaMK after binding to the Ca2+ binding protein Calmodulin. The Ca2+/CaM complex then activates CaMK and causes various cellular responses, such as smooth muscle contractions, or induces the activation of several different types of enzymes, such as NOS or PI3K. DAG causes protein kinase C (PKC) activation and also various cellular responses.

Additional pathways activated through the OTR include the MAP-kinase (MAPK) and the Rho kinase pathways. The increased transcription of COX2 mediates the increased production and secretion of prostaglandins. The OTR-mediated opening of Ca2+ channels is likely mediated through free Gβγ subunits. The OT receptor is known to be coupled with the other G proteins, Gs and Gi, both of which are linked with the AC pathway.

The proliferative effects involve MAPK-mediated activation of specific gene transcription.

The trophic effects are mediated via a PKC-mediated activation of eEF2. Activation of the Rho and MAP kinase pathways, the increase in intracellular Ca2+ and the increased prostaglandin secretion all contribute to the contractile effects. The antiproliferative effects observed in certain cells types appear to be mediated via αi G protein subunits.

1. The Gi mediated anti-proliferative effect has been described as dependent on epidermal growth factor receptor (EGFR) transactivation and mitogen-activated protein kinase (MAPK) activation via a PLC/PI3K/cellular sarcoma tyrosine kinase (c-Src)-dependent pathway that ultimately leads to a sustained activation of the cell cycle inhibitor.

• The mechanisms of the oxytocin-induced membrane depolarization have been explored in various types of neuronal cells, and they are classified as follows:

1. Suppression of voltage-gated K+ currents
2. Activation of non-selective cationic currents
3. Activation of sustained Na+-dependent currents (could be the same as 2)Inhibition of GABAA receptors (this would depolarize if GABA acts as a tonic inhibitory modulator).

Legend:

• solid red lines = activation
• broken blue lines = inhibition
• VGCC = Voltage-gated Ca2+ channel
• InsP3R = InsP3 receptor
• RyR = Ryanodine receptor
• PLC = Phospholipase C
• DAG = Diacyl glycerol
• Ca2+/CaM = Ca2+-calmodulin complex
• CaMK = Ca2+/Calmodulin-dependent protein kinase
• NOS = NO synthase
• PLA2= Phospholipase A2
• COX2 = Cyclooxygenase 2
• AC = Adenylate cyclase
• PI3K = Phosphoinositide 3-kinase
• ROK = Rho kinase.