RESUMO
This study was designed to determine the effects of bombesin-like peptides (BLPs) on the secretion of growth hormone (GH) and to characterize the receptor subtypes mediating these effects in cattle. Four experiments were conducted: (1) six steers were randomly assigned to receive intravenous (IV) bolus injections of 0, 0.2, 1.0, 12.5 and 50.0 µg/kg neuromedin C (NMC); (2) seven pre-weaned calves were IV injected with 1.0 µg/kg NMC; (3) six steers were IV injected with 2.5µg/kg bovine gastrin-releasing peptide (GRP), 1.0 µg/kg NMC combined with 20.0 µg/kg [d-Lys(3)]-GHRP-6 (an antagonist for the GH secretagogue receptor type 1a [GHS-R1a]), 1.0 µg/kg NMC combined with 20.0 µg/kg N-acetyl-GRP(20-26)-OCH(2)CH(3) (N-GRP-EE, an antagonist for the GRP receptor), 20.0 µg/kg N-GRP-EE alone, 1.0 µg/kg neuromedin B (NMB); and (4) four rats were IV injected 1.0 µg/kg NMC. A serial blood sample was collected before and after injection. Plasma GH levels dose-dependently increased at 5 min after NMC injection and the minimal effective dose was 1.0 µg/kg. Plasma GH level was elevated by GRP, but not by NMB. The NMC-induced elevation of GH was completely blocked by N-GRP-EE. The administration of NMC elevated GH level in pre-weaned calves but not in rats. Ghrelin level was unaffected by any treatments; and [d-Lys(3)]-GHRP-6 did not block the NMC-induced elevation of GH. The results indicate BLP-induced elevation of GH levels is mediated by the GRP receptor but not through a ghrelin/GHS-R1a pathway in cattle.
Assuntos
Bombesina/farmacologia , Peptídeo Liberador de Gastrina/farmacologia , Hormônio do Crescimento/metabolismo , Fragmentos de Peptídeos/farmacologia , Receptores da Bombesina/metabolismo , Sequência de Aminoácidos , Animais , Bombesina/administração & dosagem , Bombesina/química , Bovinos , Relação Dose-Resposta a Droga , Peptídeo Liberador de Gastrina/administração & dosagem , Peptídeo Liberador de Gastrina/química , Grelina/sangue , Grelina/metabolismo , Hormônio do Crescimento/sangue , Masculino , Dados de Sequência Molecular , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/química , Ratos , Ratos Wistar , Receptores da Bombesina/antagonistas & inibidoresRESUMO
The effect of appetite regulatory hormone cholecystokinin (CCK) on the secretions of oxyntomodulin (OXM) and ghrelin, and the effect of ghrelin on the secretions of CCK and OXM were studied in ruminants. Eight Holstein steers, 7 months old, 243 ± 7 kg body weight (BW), were arranged in an incomplete Latin square design (8 animals × 4 treatments × 4 days of sampling). Steers were intravenously injected with 10 µg of sulfated CCK-8/kg BW, 20 µg of acyl ghrelin/kg BW, 100 µg of des-acyl ghrelin/kg BW or vehicle. Blood samples were collected from -60 min to 120 min relative to time of injection. Plasma concentrations of ghrelin, sulfated CCK and OXM were measured by double-antibody radioimmunoassay. Plasma acyl ghrelin was increased to peak level (428.3 ± 6 pg/mL) at 60 min after injection of CCK compared with pre-injected levels (203.3 ± 1 pg/mL). These results showed for the first time, that intravenous bolus injection of CCK increased ghrelin secretion in ruminants. In contrast, injection of ghrelin did not change CCK secretion. Administration of ghrelin or CCK has no effect on plasma OXM concentrations. In conclusion, our results show that administration of CCK increased ghrelin secretion but did not affect OXM release in ruminants. Ghrelin did not affect the secretions of CCK and OXM.
Assuntos
Bovinos/fisiologia , Colecistocinina/farmacologia , Grelina/metabolismo , Fragmentos de Peptídeos/farmacologia , Estômago de Ruminante/metabolismo , Animais , Colecistocinina/administração & dosagem , Grelina/sangue , Grelina/farmacologia , Grelina/fisiologia , Injeções Intravenosas , Insulina/sangue , Masculino , Oxintomodulina/sangue , Oxintomodulina/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Radioimunoensaio/métodos , Estimulação QuímicaRESUMO
This study was designed to determine the effects of gastrin on the circulating levels of ghrelin, growth hormone (GH), insulin, glucagon and glucose in ruminants. Two experiments were done in eight Holstein steers. Animals were randomly assigned to receive intravenous bolus injections: (1) 0.1% bovine serum albumin in saline as vehicle, 0.8, 4.0 and 20.0 µg/kg body weight (BW) of bovine sulfated gastrin-34; (2) vehicle, 0.53 µg/kg BW of bovine sulfated gastrin-17 alone or combined with 20.0 µg/kg BW of [D-Lys(3)]-GHRP-6, the selective antagonist of GHS-R1a. Blood samples were collected from -10 to 150 min relative to injection time. Concentrations of acyl and total ghrelin in response to gastrin-34 injection were significantly increased in a dose-dependent manner. Concentrations of GH were also markedly elevated by gastrin-34 injection; however, the effect of 20.0 µg/kg was weaker than that of 4.0 µg/kg. The three doses of gastrin-34 equally decreased insulin levels within 15 min and maintained the level until the time of last sampling. Gastrin-34 had no effect (P > 0.05) on the levels of glucagon and glucose. Levels of acyl ghrelin increased after administration of gastrin-17 alone or combined with [D-Lys(3)]-GHRP-6; however, [D-Lys(3)]-GHRP-6 did not block the elevation of GH by gastrin-17. The present results indicate that sulfated gastrin stimulates both ghrelin and GH release, but the GHS-R1a may not contribute to the release of GH by gastrin. Moreover, sulfated gastrin seems to indirectly maintain the homeostasis of blood glucose through the down-regulation of insulin in ruminants.
Assuntos
Gastrinas/administração & dosagem , Grelina/sangue , Hormônio do Crescimento/sangue , Precursores de Proteínas/administração & dosagem , Ruminantes/fisiologia , Transdução de Sinais/fisiologia , Estômago de Ruminante/fisiologia , Animais , Glicemia/metabolismo , Bovinos , Relação Dose-Resposta a Droga , Grelina/metabolismo , Glucagon/sangue , Glucagon/metabolismo , Hormônio do Crescimento/metabolismo , Injeções Intravenosas , Insulina/sangue , Insulina/metabolismo , Secreção de Insulina , Masculino , Transdução de Sinais/efeitos dos fármacos , Estômago de Ruminante/efeitos dos fármacos , Sulfatos/metabolismoRESUMO
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.