Melanopsin mediates light-dependent relaxation in blood vessels

Gautam Sikka, G. Patrick Hussmann, Deepesh Pandey, Suyi Cao, Daijiro Hori, Jong Taek Park, Jochen Steppan, Jae Hyung Kim, Viachaslau Barodka, Allen C. Myers, Lakshmi Santhanam, Daniel Nyhan, Marc K. Halushka, Raymond C. Koehler, Solomon H. Snyder, Larissa A. Shimoda, Dan E. Berkowitz

Research output: Contribution to journalArticlepeer-review

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 associatedwith 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, lightactivated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor.

Original languageEnglish (US)
Pages (from-to)17977-17982
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number50
DOIs
StatePublished - Dec 16 2014

Keywords

  • GRK2
  • Melanopsin
  • Opsin
  • Photorelaxation
  • Signal transduction

ASJC Scopus subject areas

  • General

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