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Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):17977-82. doi: 10.1073/pnas.1420258111. Epub 2014 Nov 17.

Melanopsin mediates light-dependent relaxation in blood vessels.

Author information

1
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287;
2
Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205;
3
Department of Surgery, Johns Hopkins University, Baltimore, MD 21287;
4
Department of Allergy and Immunology, Johns Hopkins University, Baltimore, MD 21224;
5
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205;
6
Department of Pathology, Johns Hopkins University, Baltimore, MD 21287; and.
7
Department of Pathology, Johns Hopkins University, Baltimore, MD 21287; and ssnyder@jhmi.edu dberkow1@jhmi.edu.
8
Division of Pulmonary Medicine, Johns Hopkins University, Baltimore, MD 21224.
9
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205; ssnyder@jhmi.edu dberkow1@jhmi.edu.

Abstract

Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral responses to light, including circadian photo-entrainment, light suppression of activity in nocturnal animals, and alertness in diurnal animals. We report a physiological role for Opn4 in regulating blood vessel function, particularly in the context of photorelaxation. Using PCR, we demonstrate that Opn4 (a classic G protein-coupled receptor) is expressed in blood vessels. Force-tension myography demonstrates that vessels from Opn4(-/-) mice fail to display photorelaxation, which is also inhibited by an Opn4-specific small-molecule inhibitor. The vasorelaxation is wavelength-specific, with a maximal response at ∼430-460 nm. Photorelaxation does not involve endothelial-, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling but is associated with vascular hyperpolarization, as shown by intracellular membrane potential measurements. Signaling is both soluble guanylyl cyclase- and phosphodiesterase 6-dependent but protein kinase G-independent. β-Adrenergic receptor kinase 1 (βARK 1 or GRK2) mediates desensitization of photorelaxation, which is greatly reduced by GRK2 inhibitors. Blue light (455 nM) regulates tail artery vasoreactivity ex vivo and tail blood blood flow in vivo, supporting a potential physiological role for this signaling system. This endogenous opsin-mediated, light-activated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor.

KEYWORDS:

GRK2; melanopsin; opsin; photorelaxation; signal transduction

Comment in

PMID:
25404319
PMCID:
PMC4273372
DOI:
10.1073/pnas.1420258111
[Indexed for MEDLINE]
Free PMC Article

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