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2014 ; 111
(50
): 17977-82
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Melanopsin mediates light-dependent relaxation in blood vessels
#MMPMID25404319
Sikka G
; Hussmann GP
; Pandey D
; Cao S
; Hori D
; Park JT
; Steppan J
; Kim JH
; Barodka V
; Myers AC
; Santhanam L
; Nyhan D
; Halushka MK
; Koehler RC
; Snyder SH
; Shimoda LA
; Berkowitz DE
Proc Natl Acad Sci U S A
2014[Dec]; 111
(50
): 17977-82
PMID25404319
show ga
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.
?-Adrenergic receptor kinase 1 (?ARK 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.
|*Light
[MESH]
|Animals
[MESH]
|Blood Vessels/metabolism/*physiology
[MESH]
|Blotting, Western
[MESH]
|Cyclic GMP/metabolism
[MESH]
|Cyclic Nucleotide Phosphodiesterases, Type 6/metabolism
[MESH]