Endothelin Modulates Chemoreceptor Cell Function in Mammalian Carotid Body

Abstract

The endothelins (ET-1, ET-2, ET-3), a family of unique 21 amino acid peptides, produce a transient vasodilation and protracted vasoconstriction in numerous vascular beds (see Rubanyi and Polokoff, 1994, for review). The synthesis and release of ETs was first described in cultured vascular endothelial cells, but later studies showed that ETs and specific ET receptor sites also exist in the peripheral and central nervous systems, suggesting that in addition to their role as local vasoactive agents, ETs may also function as neuropeptides (Greenberg et al, 1992; Rubanyi and Polokoff, 1994). The tissue distribution of ETs indicates that they frequently co-occur with two other potent vasoactive agents, atrial natriuretic peptide (ANP) and nitric oxide (NO). There are important interactions between these agents, and in some cases ETs are uniquely antagonistic to the physiological effects of NO and ANP (Rubanyi and Polokoff, 1994). Biochemical assessments of the signal transduction mechanisms employed by these agents have shown that the actions of ANP and NO result from increased cyclic GMP (cGMP) production and decreased cellular [Ca²⁺]_i (e.g., see White et al, 1993), whereas the effects of ETs are mediated by elevated inositol phosphate (IPn), protein kinase C (PKc) and sometimes cAMP production, with consequent increases in [Ca²⁺]_i (Simonson & Dunn, 1990; Rubanyi & Polokoff, 1994).