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10.1073/pnas.1420258111

http://scihub22266oqcxt.onion/10.1073/pnas.1420258111
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suck abstract from ncbi


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pmid25404319
      Proc+Natl+Acad+Sci+U+S+A 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]
  • |G-Protein-Coupled Receptor Kinase 2/metabolism [MESH]
  • |Laser-Doppler Flowmetry [MESH]
  • |Mice [MESH]
  • |Myography [MESH]
  • |Reverse Transcriptase Polymerase Chain Reaction [MESH]
  • |Rod Opsins/*metabolism [MESH]
  • |Signal Transduction/*physiology [MESH]


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