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

Nathaniel York; Patrick Halbach; Michelle A Chiu; Ian M Bird; De-Ann M Pillers; Bikash R Pattnaik

doi:10.1016/j.cellsig.2017.06.005

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

Cell Signal. 2017 Sep:37:93-102. doi: 10.1016/j.cellsig.2017.06.005. Epub 2017 Jun 8.

Authors

Nathaniel York¹, Patrick Halbach¹, Michelle A Chiu², Ian M Bird³, De-Ann M Pillers⁴, Bikash R Pattnaik⁵

Affiliations

¹ Endocrinology-Reproductive Physiology Program, The University of Wisconsin, Madison, WI 53715, United States; Division of Neonatology& Newborn Nursery, The University of Wisconsin, Madison, WI 53715, United States; Departments of Pediatrics, The University of Wisconsin, Madison, WI 53715, United States; The McPherson Eye Research Institute, The University of Wisconsin, Madison, WI 53715, United States.
² Division of Neonatology& Newborn Nursery, The University of Wisconsin, Madison, WI 53715, United States; Departments of Pediatrics, The University of Wisconsin, Madison, WI 53715, United States; The McPherson Eye Research Institute, The University of Wisconsin, Madison, WI 53715, United States.
³ Endocrinology-Reproductive Physiology Program, The University of Wisconsin, Madison, WI 53715, United States; Obstetrics & Gynecology, The University of Wisconsin, Madison, WI 53715, United States.
⁴ Division of Neonatology& Newborn Nursery, The University of Wisconsin, Madison, WI 53715, United States; Departments of Pediatrics, The University of Wisconsin, Madison, WI 53715, United States; Medical Genetics, The University of Wisconsin, Madison, WI 53715, United States; The McPherson Eye Research Institute, The University of Wisconsin, Madison, WI 53715, United States.
⁵ Endocrinology-Reproductive Physiology Program, The University of Wisconsin, Madison, WI 53715, United States; Division of Neonatology& Newborn Nursery, The University of Wisconsin, Madison, WI 53715, United States; Departments of Pediatrics, The University of Wisconsin, Madison, WI 53715, United States; Ophthalmology &Visual Sciences, The University of Wisconsin, Madison, WI 53715, United States; The McPherson Eye Research Institute, The University of Wisconsin, Madison, WI 53715, United States. Electronic address: pattnaik@wisc.edu.

Abstract

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.

Keywords: Calcium imaging; Cell signaling; Hormone receptor; Inositol 1,4,5-trisphosphate (IP3); Ion-channel; Oxytocin; Oxytocin receptor; RPE; Retina.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium / metabolism*
Cell Line
Cells, Cultured
HEK293 Cells
Humans
Mice, Inbred C57BL
Oxytocin / metabolism*
Phosphatidylinositol 4,5-Diphosphate / metabolism*
Potassium Channels, Inwardly Rectifying / metabolism*
Receptors, Oxytocin / metabolism*
Retinal Pigment Epithelium / metabolism*
Signal Transduction*

Substances

Kir7.1 channel
Phosphatidylinositol 4,5-Diphosphate
Potassium Channels, Inwardly Rectifying
Receptors, Oxytocin
Oxytocin
Calcium

Abstract

Publication types

MeSH terms

Substances

Grants and funding