Melanopsin mediates light-dependent relaxation in blood vessels

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Vessels / metabolism
  • Blood Vessels / physiology*
  • Blotting, Western
  • Cyclic GMP / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 6 / metabolism
  • G-Protein-Coupled Receptor Kinase 2 / metabolism
  • Laser-Doppler Flowmetry
  • Light*
  • Mice
  • Myography
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rod Opsins / metabolism*
  • Signal Transduction / physiology*
  • Vasodilation / physiology*
  • Vasodilation / radiation effects


  • Rod Opsins
  • melanopsin
  • GRK2 protein, mouse
  • G-Protein-Coupled Receptor Kinase 2
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • Cyclic GMP