Involvement of endothelin B receptors in the endothelin-3-induced increase of ghrelin and growth hormone in Holstein steers

The present study was designed to determine the dose-dependent effects of endothelin-3 (ET-3) on the secretion of ghrelin and growth hormone (GH) and characterize the receptors involved in these effects. Eight Holstein steers were randomly assigned to receive intravenous bolus injections of vehicle (0.1% bovine serum albumin in saline), bovine ET-3 (0.1, 0.4, 0.7 and 1.0 μg/kg), IRL1620 (selective ETB receptor agonist, 2.0 μg/kg), [d-Lys3]-GHRP-6 (GH secretagogue receptor type 1a [GHS-R1a] antagonist, 20.0 μg/kg) and bovine ET-3 (1.0 μg/kg) combined with [d-Lys3]-GHRP-6 (20.0 μg/kg), respectively. Blood samples were collected at −30, −15, 0, 5, 10, 15, 20, 25, 30, 35, 40, 50 and 60 min relative to injection time. Concentrations of acyl ghrelin, total ghrelin (acyl and des-acyl ghrelin) and GH in plasma were analyzed by a double antibody radioimmunoassay system. Concentrations of acyl and total ghrelin were significantly increased by ET-3 in a dose-dependent manner. Concentrations of GH were markedly elevated by administration of 0.4, 0.7 and 1.0 μg/kg of ET-3, and the effect of 0.7 μg/kg was greater than that of 1.0 μg/kg. The minimum effective dose of ET-3 in the secretion of ghrelin and GH was 0.4 μg/kg. IRL 1620 mimicked the effects of ET-3 on the secretion of ghrelin and GH in plasma. ET-3-induced elevation of plasma GH was blocked by [d-Lys3]-GHRP-6. These results indicate that ET-3 dose-dependently stimulates ghrelin release, and ETB receptors involve in these processes. Moreover, this study shows that endogenous ghrelin response to ET-3 increases GH secretion through GHS-R1a.