| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Santhanam, Lakshmi Park, Jong Taek Sikka, Gautam Koehler, Raymond C. Snyder, Solomon H. Myers, Allen C. Nyhan, Daniel Hussmann, G. Patrick Barodka, Viachaslau Halushka, Marc K. Hori, Daijiro Berkowitz, Dan E. Pandey, Deepesh Cao, Suyi Kim, Jae Hyung Steppan, Jochen Shimoda, Larissa A. |
| Description |
Author Affiliation: 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); 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); 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); 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); |
| 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 â ¼430-460 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. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
50 |
| Volume Number |
111 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2014-12-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Blood Vessels Physiology Rod Opsins Metabolism Signal Transduction Vasodilation Animals Blotting, Western Cyclic GMP Cyclic Nucleotide Phosphodiesterases, Type 6 G-Protein-Coupled Receptor Kinase 2 Laser-Doppler Flowmetry Mice Myography Reverse Transcriptase Polymerase Chain Reaction Radiation Effects Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
