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

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.

Author information

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

PMID:
28603013
PMCID:
PMC5554455
DOI:
10.1016/j.cellsig.2017.06.005
[Indexed for MEDLINE]
Free PMC Article

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