title: Pharmacological induction of skin pigmentation unveils the neuroendocrine circuit regulated by light.
abstract: Light-regulated skin colour change is an important physiological process in invertebrates and lower vertebrates, and includes daily circadian variation and camouflage (i.e. background adaptation). The photoactivation of melanopsin-expressing retinal ganglion cells (mRGCs) in the eye initiates an uncharacterized neuroendocrine circuit that regulates melanin dispersion/aggregation through the secretion of alpha-melanocyte-stimulating hormone (α-MSH). We developed experimental models of normal or enucleated Xenopus embryos, as well as in situ cultures of skin of isolated dorsal head and tails, to analyse pharmacological induction of skin pigmentation and α-MSH synthesis. Both processes are triggered by a melanopsin inhibitor, AA92593, as well as chloride channel modulators. The AA9253 effect is eye-dependent, while functional data in vivo point to GABAA receptors expressed on pituitary melanotrope cells as the chloride channel blocker target. Based on the pharmacological data, we suggest a neuroendocrine circuit linking mRGCs with α-MSH secretion, which is used normally during background adaptation.
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Gabriel E
authors.initials: GE
authors.lastname: Bertolesi
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Sherene T
authors.initials: ST
authors.lastname: Vazhappilly
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Hehr
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: McFarlane
mesh_terms: D000818:Animals; D008027:Light; D055099:Neuroendocrine Cells / Q000166:cytology / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000166:cytology / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D017299:Rod Opsins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012880:Skin Pigmentation / Q000187:drug effects / Q000528:radiation effects; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014982:Xenopus laevis; D000521:alpha-MSH / Q000378:metabolism*; D000099210:Melanopsin
chemical_list: D017299:Rod Opsins; D029867:Xenopus Proteins; D000521:alpha-MSH; D000099210:Melanopsin
keywords: Xenopus; alpha-melanocyte-stimulating hormone; ivermectin; melanopsin; picrotoxin