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Melanopsin mediates light-dependent relaxation in blood vessels.
Sikka, Gautam; Hussmann, G Patrick; Pandey, Deepesh; Cao, Suyi; Hori, Daijiro; Park, Jong Taek; Steppan, Jochen; Kim, Jae Hyung; Barodka, Viachaslau; Myers, Allen C; Santhanam, Lakshmi; Nyhan, Daniel; Halushka, Marc K; Koehler, Raymond C; Snyder, Solomon H; Shimoda, Larissa A; Berkowitz, Dan E.
Afiliación
  • Sikka G; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287;
  • Hussmann GP; Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205;
  • Pandey D; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287;
  • Cao S; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287;
  • Hori D; Department of Surgery, Johns Hopkins University, Baltimore, MD 21287;
  • Park JT; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287;
  • Steppan J; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287;
  • Kim JH; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287;
  • Barodka V; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287;
  • Myers AC; Department of Allergy and Immunology, Johns Hopkins University, Baltimore, MD 21224;
  • Santhanam L; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205;
  • Nyhan D; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287;
  • Halushka MK; Department of Pathology, Johns Hopkins University, Baltimore, MD 21287; and.
  • Koehler RC; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287;
  • Snyder SH; Department of Pathology, Johns Hopkins University, Baltimore, MD 21287; and ssnyder@jhmi.edu dberkow1@jhmi.edu.
  • Shimoda LA; Division of Pulmonary Medicine, Johns Hopkins University, Baltimore, MD 21224.
  • Berkowitz DE; 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.
Proc Natl Acad Sci U S A ; 111(50): 17977-82, 2014 Dec 16.
Article en En | MEDLINE | ID: mdl-25404319
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. ß-Adrenergic receptor kinase 1 (ßARK 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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Vasodilatación / Vasos Sanguíneos / Transducción de Señal / Opsinas de Bastones / Luz Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2014 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Vasodilatación / Vasos Sanguíneos / Transducción de Señal / Opsinas de Bastones / Luz Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2014 Tipo del documento: Article