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 1.0microg/kg), IRL1620 (selective ET(B) receptor agonist, 2.0microg/kg), [d-Lys(3)]-GHRP-6 (GH secretagogue receptor type 1a [GHS-R1a] antagonist, 20.0microg/kg) and bovine ET-3 (1.0microg/kg) combined with [d-Lys(3)]-GHRP-6 (20.0microg/kg), respectively. Blood samples were collected at -30, -15, 0, 5, 10, 15, 20, 25, 30, 35, 40, 50 and 60min 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 1.0microg/kg of ET-3, and the effect of 0.7microg/kg was greater than that of 1.0microg/kg. The minimum effective dose of ET-3 in the secretion of ghrelin and GH was 0.4microg/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-Lys(3)]-GHRP-6. These results indicate that ET-3 dose-dependently stimulates ghrelin release, and ET(B) receptors involve in these processes. Moreover, this study shows that endogenous ghrelin response to ET-3 increases GH secretion through GHS-R1a.
Department of Life Science and Agriculture, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-11, Inada, Obihiro 080-8555, Japan. zhaohongqiong@sina.com
Hongqiong
H
Zhao
Sint
S
Thanthan
Swe
S
Yannaing
Hideto
H
Kuwayama
D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D019334:Endothelin-3 / Q000494:pharmacology*; D016232:Endothelins / Q000097:blood / Q000494:pharmacology; D054439:Ghrelin / Q000097:blood*; D013006:Growth Hormone / Q000097:blood*; D010446:Peptide Fragments / Q000494:pharmacology; D011863:Radioimmunoassay; D044023:Receptor, Endothelin B / Q000819:agonists / Q000378:metabolism*; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D019334:Endothelin-3; D016232:Endothelins; D054439:Ghrelin; D010446:Peptide Fragments; D044023:Receptor, Endothelin B; D054440:Receptors, Ghrelin; C074308:sovateltide; D013006:Growth Hormone