PDE and sGC hand in hand to see the light.

In PNAS, Sikka et al. (1) suggest that melanopsin, a non–image-forming opsin (opsin4, Opn4), may play a physiological role in the regulation of vascular tone by mediating photorelaxation. The authors conclude that the response to light is due to hyperpolarization of the vascular smooth muscle cells resulting from the activation of soluble guanylyl cyclase (sGC), but does not involve protein kinase G (PKG). This study not only provides an intriguing molecular explanation for a phenomenon (photorelaxation) that has puzzled vascular biologists for more than half a century (2), but also forces us to rethink the fate of the products generated by sGC.