Ocular Actions of Endothelins

Abstract

Endothelins (ETs) represent a group of 21 amino acid-containing peptides that include two disulfide bridges. Endothelin was first isolated as the potent vasoconstrictor from supernatants of cultured endothelial cells (1) and appears to be evolutionary related to a group of snake venoms that includes sarafo-toxin S6c. Endothelin's vasoconstrictor activity is 10 times that of angiotensin II (2). These potent vasoconstrictors are important endogenous vascular mediators that are released in response to certain factors or during cell injury. It appears that the structures of ET are conserved among the different species, such that ET-1 in the human is identical to that in the rat. This conservation may be reflective of the critical role ET plays in vascular homeostasis. Three structurally and pharmacologically different peptides have been prepared based on genetic sequence information determined by molecular cloning techniques (3). Each of these peptides have different pharmacological profiles, tissue localization, and cellular actions (Table I). Endothelin-1 appears to have the greatest distribution in tissues and is a constituent of plasma. The concentration of ET in plasma varies between 0.26 and 5 pg/ml (4, 5) and may reach 35 pg/ ml during some cardiovascular pathologies. The source of this ET is thought to be the vascular endothelial cells. However, the identification of ET and its precursor peptide in other tissues suggests that it may come from more than one source.

Endothelin effects have been considered to be either autocrine, paracrine, or endocrine, depending on the tissue responses measured. It is clear, however, that the discovery of this potent peptide has led to many speculations concerning its endogenous role and function. For this review we have concentrated on ET's actions in ocular tissues. Because of the limited scope of this review, we have focused on the most recent findings in this area. We apologize in advance for having restricted our references and may have inadvertently failed to recognize everyone's contribution. For further detailed reviews of ETs vascular and nonvascular pharmacological actions, see Refs. 6 and 7.