Oxytocin (OXT)-stimulated inhibition of Kir7.1 activity is through PIP 2 -dependent Ca 2+ response of the oxytocin receptor in the retinal pigment epithelium in vitro

Abstract

<p class="first" id="P1">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 [Ca ²⁺] _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 Ca ²⁺ signaling to demonstrate that OXTR utilizes capacitative Ca ²⁺ entry (CCE) mechanisms to sustain an increase in cytoplasmic Ca ²⁺. 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. </p>