Oxytocin (OXT)-stimulated inhibition of Kir7.1 activity is through PIP2-dependent Ca2+ response of the oxytocin receptor in the retinal pigment epithelium in vitro

• Published in: Cellular signalling 2017-09, Vol.37, p.93-102
• Main Authors: York, Nathaniel, Halbach, Patrick, Chiu, Michelle A., Bird, Ian M., Pillers, De-Ann M., Pattnaik, Bikash R.
• Format: Article
• Language: English
• Subjects: Calcium imaging; Cell signaling; Hormone receptor; Inositol 1,4,5-trisphosphate (IP3); Ion-channel; Oxytocin; Oxytocin receptor; Retina; RPE
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2017.06.005

Oxytocin (OXT) is a neuropeptide that activates the oxytocin receptor (OXTR), a rhodopsin family G-protein coupled receptor. Our localization of OXTR to the retinal pigment epithelium (RPE), in close proximity to OXT in the adjacent photoreceptor neurons, leads us to propose that OXT plays an important role in RPE-retinal communication. An increase of RPE [Ca2+]i in response to OXT stimulation implies that the RPE may utilize oxytocinergic signaling as a mechanism by which it accomplishes some of its many roles. In this study, we used an established human RPE cell line, a HEK293 heterologous OXTR expression system, and pharmacological inhibitors of Ca2+ signaling to demonstrate that OXTR utilizes capacitative Ca2+ entry (CCE) mechanisms to sustain an increase in cytoplasmic Ca2+. These findings demonstrate how multiple functional outcomes of OXT-OXTR signaling could be integrated via a single pathway. In addition, the activated OXTR was able to inhibit the Kir7.1 channel, an important mediator of sub retinal waste transport and K+ homeostasis. •OXT-OXTR signaling is complex and although it is universally accepted that OXT-OXTR utilizes GPCR mechanism, there is debate and it is perhaps a tissue dependent signaling mechanism.•Cell signaling between cone photoreceptor and RPE is not well studied due to the abundance of rod photoreceptor in laboratory mammals.•Visual demonstration of OXT-OXTR activated phosphoinositide hydrolysis induced by PLC activation has not been established using single-cell microscopy.•Downstream effect of OXT-OXTR signaling is limited to InsP3 or Ca2+ or activation of protein kinases.•Regulation of ion-channels like Kir7.1 by GPCR is an emerging field of research.