Growth Hormone-Independent Cardioprotective Effects of Hexarelin in the Rat1

Locatelli,; Rossoni, Giuseppe; Schweiger, F; Torsello, Antonio; Colonna, De Gennaro; Bernareggi, Micaela; Deghenghi, Romano; Ee, Müller; Berti, F.

doi:10.1210/endo.140.9.6948

Cited by 111 publications

(10 citation statements)

References 31 publications

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“…Despite the apparently low levels of GHS-R mRNA in the heart, a number of studies show that both ghrelin and GHSs influence a variety of cardiovascular functions, such as myocardial contractility [44], vasodilatation [47] and protection from myocardial infarction-induced heart failure in vivo [44,48,49]. In summary, the current opinion still is that the positive influence of GHS on cardiac functions is probably mediated by GHS-R1a.…”

Section: Ghs-r Actions In the Cardiovascular Systemmentioning

confidence: 99%

Growth Hormone Secretagogue (Ghrelin-) Receptors - A Complex Drug Target for the Regulation of Body Weight

Nogueiras¹,

Pérez-Tilve²,

Wortley³

et al. 2006

CNSNDDT

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The growth hormone secretagogue receptor (GHS-R) is expressed in several tissues and seems to mediate the different actions of the synthetic growth hormone secretagogues (GHS) and the endogenous ligand of this receptor, ghrelin. The GHS-R belongs to the family of G-protein coupled receptors (GPCR). Two different receptor variants, type 1a and 1b, have been described and they seem to mediate different actions in different tissues. In addition to their functions on growth hormone (GH) secretion and food intake, ghrelin and its receptor are involved in several cardiovascular mechanisms, pancreatic functions, adipogenesis, gonadal function, immune system actions or tumoral cells. This review will summarize data regarding the structure of the GHS-R gene, reports investigating the expression, control and functions of the GHS-R in various tissues, and studies of the underlying transcriptional mechanisms and the genetic manipulation of both ghrelin and GHS-R. Thus, it seems clear the possibility that ghrelin and/or GHS analogs, acting as either agonists or antagonists on different activities, might have clinical impact.

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Section: Ghs-r Actions In the Cardiovascular Systemmentioning

confidence: 99%

Growth Hormone Secretagogue (Ghrelin-) Receptors - A Complex Drug Target for the Regulation of Body Weight

Nogueiras¹,

Pérez-Tilve²,

Wortley³

et al. 2006

CNSNDDT

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“…Since the discovery of the first GHS derived from the pentapeptide met-enkephaline [2], various peptide and non-peptide compounds with different GH-releasing potency have been developed. Current studies on the characterization of the biological properties of these compounds have reported that, in addition to their GH stimulatory activity, some GHS are able to play a role in the control of sleep [3], cardiac function [4], male sexual behavior [5]and food intake [6]. The expanded functional role of GHS is supported by the evidence that mRNA for GHS-R is widely expressed in the CNS and in several peripheral tissues [7].…”

Section: Introductionmentioning

confidence: 99%

Evidence for a Central Inhibitory Role of Growth Hormone Secretagogues and Ghrelin on Gastric Acid Secretion in Conscious Rats

Sibilia

Pagani²,

Guidobono³

et al. 2002

Neuroendocrinology

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We examined the possible central and peripheral effects of synthetic growth hormone secretagogues (GHS), hexarelin (Hexa) and EP 40737 (D-Thr-D-Trp (2-Me)-Ala- Trp-D-Phe-Lys-NH₂), and of their endogenous counterpart, ghrelin, on gastric acid secretion. The compounds were administered intracerebroventricularly (i.c.v.) or subcutaneously (s.c.) in conscious male rats and the volume of gastric secretion and gastric acid output were examined 3 h after pylorus ligation (Shay-test). Central Hexa, EP 40737 and ghrelin administration (from 0.1 pmol to 1 nmol/rat, i.c.v.) significantly inhibited gastric acid secretion. The maximum inhibitory effect on gastric acid output was detected at the dose of 10 pmol/rat, i.c.v. for Hexa (–51.3%), of 100 pmol/rat, i.c.v. for EP 40737 (–70%) and of 1 pmol/rat, i.c.v. for ghrelin (–60%). All peptides were less effective at the highest dose used (1 nmol/rat, i.c.v.). Hexa, EP 40737 and ghrelin injected s.c. did not modify gastric acid secretion. The inhibitory action of Hexa on gastric acid secretion seems to involve brain somatostatinergic system since Hexa (10 pmol/rat, i.c.v.) did not inhibit gastric acid secretion in rats pretreated (4 h before) with cysteamine (300 mg/kg, s.c.), a depletor of endogenous somatostatin. These results show that synthetic GHS and ghrelin exert a central long-lasting inhibitory effect on gastric acid secretion in conscious pylorus-ligated rats. The fact that very low doses of ghrelin and GHS inhibit gastric secretion, provide evidence for a tonic inhibitory role of the peptides in the central control of gastric secretory function.

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“…Pre-administration of ghrelin in vivo greatly ameliorated the damaged heart function, attenuated myocardial injury, and apoptosis through inhibition of ER stress [170]. The role of hexarelin on the protection against cardiac ischemia has been reported earlier [67,68,171]. Rats pre-treated with ghrelin or hexarelin for 7 days in vivo prior to in vitro I/R injury showed an improvement in cardiac function [172].…”

Section: Ghrelin and Hexarelin Promote Mitochondrial Activity And Biomentioning

confidence: 90%

“…Hexarelin has many physiological actions independent of growth hormone such as the protection against cardiac ischemia and impairment of vascular endothelium function in the hearts of GH-deficient rats [67,68]. GHS-R1a seems to mediate the action of hexarelin.…”

Section: Growth Hormone Secretagogues (Ghs)mentioning

confidence: 99%

Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases

et al. 2015

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Ghrelin and its synthetic analog hexarelin are specific ligands of growth hormone secretagogue (GHS) receptor. GHS have strong growth hormone-releasing effect and other neuroendocrine activities such as stimulatory effects on prolactin and adrenocorticotropic hormone secretion. Recently, several studies have reported other beneficial functions of GHS that are independent of GH. Ghrelin and hexarelin, for examples, have been shown to exert GH-independent cardiovascular activity. Hexarelin has been reported to regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) in macrophages and adipocytes. PPAR-γ is an important regulator of adipogenesis, lipid metabolism, and insulin sensitization. Ghrelin also shows protective effects on beta cells against lipotoxicity through activation of phosphatidylinositol-3 kinase/protein kinase B, c-Jun N-terminal kinase ( JNK) inhibition, and nuclear exclusion of forkhead box protein O1. Acylated ghrelin (AG) and unacylated ghrelin (UAG) administration reduces glucose levels and increases insulinproducing beta cell number, and insulin secretion in pancreatectomized rats and in newborn rats treated with streptozotocin, suggesting a possible role of GHS in pancreatic regeneration. Therefore, the discovery of GHS has opened many new perspectives in endocrine, metabolic, and cardiovascular research areas, suggesting the possible therapeutic application in diabetes and diabetic complications especially diabetic cardiomyopathy. Here, we review the physiological roles of ghrelin and hexarelin in the protection and regeneration of beta cells and their roles in the regulation of insulin release, glucose, and fat metabolism and present their potential therapeutic effects in the treatment of diabetes and diabetic-associated heart diseases. Disciplines Medicine and Health Sciences Publication DetailsMosa, R., Zhang, Z., Shao, R., Deng, C., Chen, J. & Chen, C. (2015). Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases. Endocrine, 49 (2) AbstractGhrelin and its synthetic analog hexarelin are specific ligands of growth hormone secretagogue (GHS) receptor. GHS have strong growth hormone-releasing effect and other neuroendocrine activities such as stimulatory effects on prolactin and adrenocorticotropic hormone secretion. Recently, several studies have reported other beneficial functions of GHS that are independent of GH. Ghrelin and hexarelin, for examples, have been shown to exert GH-independent cardiovascular activity. Hexarelin has been reported to regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) in macrophages and adipocytes. PPAR-γ is an important regulator of adipogenesis, lipid metabolism, and insulin sensitization. Ghrelin also shows protective effects on beta cells against lipotoxicity through activation of phosphatidylinositol-3 kinase/protein kinase B, c-Jun N-terminal kinase (JNK) inhibition, and nuclear exclusion of forkhead box protein O1. Acylated ghrelin (AG) and unacylated ghrelin (UAG) administration redu...

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Growth Hormone-Independent Cardioprotective Effects of Hexarelin in the Rat1

Cited by 111 publications

References 31 publications

Growth Hormone Secretagogue (Ghrelin-) Receptors - A Complex Drug Target for the Regulation of Body Weight

Growth Hormone Secretagogue (Ghrelin-) Receptors - A Complex Drug Target for the Regulation of Body Weight

Evidence for a Central Inhibitory Role of Growth Hormone Secretagogues and Ghrelin on Gastric Acid Secretion in Conscious Rats

Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases

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