Small-molecule antagonists of melanopsin-mediated phototransduction
| Autor: | Quansheng Zhu, Huailing Zhong, Andrew T. E. Hartwick, Satchidananda Panda, Megumi Hatori, Roman Artymyshyn, Mohammad R. Marzabadi, Kenneth A. Jones, Patricia J. Sollars, Gary E. Pickard, Sang Phyo Hong, Ludovic S. Mure, Jayne R. Bramley, Jeffrey Sprouse |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Melanopsin
medicine.medical_specialty Light Signal Transduction genetic structures Molecular neuroscience Article Small Molecule Libraries 03 medical and health sciences Structure-Activity Relationship 0302 clinical medicine Internal medicine medicine Humans Molecular Biology 030304 developmental biology 0303 health sciences Sulfonamides biology Molecular Structure Drug discovery Rod Opsins Cell Biology Small molecule Endocrinology Rhodopsin biology.protein sense organs Neuroscience 030217 neurology & neurosurgery Visual phototransduction |
| Zdroj: | Nature chemical biology |
| ISSN: | 1552-4469 |
| Popis: | Melanopsin, expressed in a subset of retinal ganglion cells, mediates behavioral adaptation to ambient light and other non-image-forming photic responses. This has raised the possibility that pharmacological manipulation of melanopsin can modulate several central nervous system responses, including photophobia, sleep, circadian rhythms and neuroendocrine function. Here we describe the identification of a potent synthetic melanopsin antagonist with in vivo activity. New sulfonamide compounds inhibiting melanopsin (opsinamides) compete with retinal binding to melanopsin and inhibit its function without affecting rod- and cone-mediated responses. In vivo administration of opsinamides to mice specifically and reversibly modified melanopsin-dependent light responses, including the pupillary light reflex and light aversion. The discovery of opsinamides raises the prospect of therapeutic control of the melanopsin phototransduction system to regulate light-dependent behavior and remediate pathological conditions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|