Endothelin Receptors: Do They Have a Role in Retinal Degeneration?

摘要

Although endothelins (ETs) were originally discovered as potent vasoconstrictors secreted by the endothelium (Yanagisawa et al., 1988), it has become evident that they also fulfill important roles in the nervous system (Schinelli, 2006). ETs are a family of 21-amino-acid peptides with three isoforms, ET-1, ET-2 and ET-3. ET-1 and ET-3 are present in most ocular structures. They are present in most regions of the anterior segment and in blood vessels of the choroid and the sclera (Chakrabarti and Sima, 1997). Precursor mRNAs of the three endothelins have been detected in the retina (Chakrabarti et al., 1998; Rattner and Nathans, 2005). ET-1 and ET-3 precursor mRNA appear in several retinal cell phenotypes (Ripodas et al., 2001), but the largest protein concentration appears in astrocytes (Torbidoni et al., 2005). ETs mediate their action through binding to two G-protein-linked receptors, ET-A and ET-B, which have been isolated and cloned from mammalian tissues (Davenport and Maguire, 2006). ET-A is characterized by the rank affinity order ET-l=ET-2>ET-3 whereas ET-B accepts all ET isopeptides with similar affinity (Kis et al., 2006). Activation of ET receptors triggers various short- and long-term changes at cellular level but their effects on brain and retinal physiology and patho-physiology are still poorly understood, since the ET system can behave completely differently in each cell type. Complex interactions occur between both endotheliner-gic receptors at different levels of the signaling pathways (Blomstrand et al., 2004), and it can sometimes be difficult to recognize receptor-specific responses. ET-B, however, is unique in its ability to internalize bound ligand, reducing extracellular levels of ETs (D'Orleans-Juste et al., 2002)