Copeptin - a long-ignored peptide hormone

Abstract Arginine vasopressin (AVP), the antidiuretic hormone secreted by hypothalamic neurons, controls water resorption and blood pressure via its receptors in the kidney and vasculature, respectively. We demonstrated and published earlier that AVP also contributes to regulating stress erythropoiesis. Vasopressin is made as part of a prohormone with a C-terminal glycopeptide which has been conserved in all of the vertebrate species studied to date. We hypothesized that this glycopeptide, copeptin (CP) might also play a role in hematopoiesis and studied this in vitro and in vivo. CP did indeed seem to be involved in hematopoiesis. Furthermore, it had a significant effect on the number and size of circulating platelets when it was injected into mice. In vitro, human platelets collected from healthy volunteers, were induced to aggregate by CP, an action that seems to result from an increase in calcium. These effects were greater when CP and AVP were given together. AVP alone is known to aggregate platelets, an action mediated by activation of AVPR1A receptors. Our results suggest that copeptin receptors should also be present on platelets, and we are searching for these. Once we find the CP receptor, we will look for its distribution in the body as a first step in understanding the biology of this forgotten hormone.