Ghrelin Prevents Cisplatin-Induced Mechanical Hyperalgesia and Cachexia (original) (raw)
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Amino Acids, 2012
Recent research suggests a role for ghrelin in the modulation of inflammatory disorders. However, the type of ghrelin receptor (GHS-R) involved in both the antiinflammatory and anti-hyperalgesic actions of ghrelin remains to be characterized. In this study, we examined whether the inhibitory effect of ghrelin in the development of hyperalgesia and edema induced by intraplantar carrageenan administration depends on an interaction with GHS-R1a. Both central (1 nmol/rat, i.c.v.) and peripheral (40 nmol/kg, i.p.) administration of the selective GHS-R1a agonist EP1572 had no effect on carrageenan-induced hyperalgesia measured by Randall-Selitto test and paw edema. Furthermore, pre-treatment with the selective GHS-R1a antagonist, D-lys 3 -GHRP-6 (3 nmol/rat, i.c.v.) failed to prevent the anti-hyperalgesic and anti-inflammatory effects exerted by central ghrelin administration (1 nmol/rat), thus indicating that the type 1a GHS-R is not involved in these peptide activities. Accordingly, both central (1 and 2 nmol/ rat, i.c.v.) and peripheral (40 and 80 nmol/kg, i.p.) administration of desacyl-ghrelin (DAG), which did not bind GHS-R1a, induced a significant reduction of the hyperalgesic and edematous activities of carrageenan. In conclusion, we have shown for the first time that DAG shares with ghrelin an inhibitory role in the development of hyperalgesia, as well as the paw edema induced by carrageenan and that a ghrelin receptor different from type 1a is involved in the anti-inflammatory activities of the peptide.
Physiological Effect of Ghrelin on Body Systems
International Journal of Endocrinology
Ghrelin is a relatively novel multifaceted hormone that has been found to exert a plethora of physiological effects. In this review, we found/confirmed that ghrelin has effect on all body systems. It induces appetite; promotes the use of carbohydrates as a source of fuel while sparing fat; inhibits lipid oxidation and promotes lipogenesis; stimulates the gastric acid secretion and motility; improves cardiac performance; decreases blood pressure; and protects the kidneys, heart, and brain. Ghrelin is important for learning, memory, cognition, reward, sleep, taste sensation, olfaction, and sniffing. It has sympatholytic, analgesic, antimicrobial, antifibrotic, and osteogenic effects. Moreover, ghrelin makes the skeletal muscle more excitable and stimulates its regeneration following injury; delays puberty; promotes fetal lung development; decreases thyroid hormone and testosterone; stimulates release of growth hormone, prolactin, glucagon, adrenocorticotropic hormone, cortisol, vasopr...
Ghrelin in Pathological Conditions
Endocrine Journal, 2008
The recently identified gastric hormone ghrelin was initially described as a natural Growth Hormone Secretagogue Receptor ligand. Apart from ghrelin's first discovered action, which was the stimulation of Growth Hormone release, implications for many other functions have been reported. It seems that ghrelin exhibits an important role in conditions related to processes regulating nutrition, body composition and growth, as well as heart, liver, thyroid or kidney dysfunction. In this review, current available knowledge about ghrelin's role in various pathological conditions is presented.
Regulatory Peptides, 2008
Chemotherapy treatment can lead to delayed gastric emptying, early satiety, anorexia, nausea and vomiting, described collectively as the cancer-associated dyspepsia syndrome (CADS). Administration of ghrelin (GHRL), an endogenous orexigenic peptide known to stimulate gastric motility, has been shown to reduce the symptoms of CADS induced in relevant animal models with the potent chemotherapeutic agent, cisplatin. We examined the effects in the rat of cisplatin (6 mg/kg i.p.) treatment on the expression of GHRL and ghrelin receptor (GHSR) mRNAs in the hypothalamus and the stomach at a time-point (2 days) when the effects of cisplatin are pronounced. In addition, plasma levels of GHRL (acylated and total including des-acyl GHRL) were measured and the effect on these levels of treatment with the synthetic glucocorticoid dexamethasone (2 mg/kg s.c. bd.) was investigated. Cisplatin increased GHSR mRNA expression in the stomach (67%) and hypothalamus (52%) but not GHRL mRNA expression and increased the percentage of acylated GHRL (7.03 ± 1.35% vs. 11.38 ± 2.40%) in the plasma. Dexamethasone reduced the plasma level of acylated GHRL and the percentage of acylated GHRL to values below those in animals treated with saline alone (7.03 ± 1.35% vs. 2.60 ± 0.49%). Our findings support the hypothesis that an adaptive upregulation of the ghrelin receptor may occur during cancer chemotherapy-associated dyspepsia. This may have a role in defensive responses to toxic challenges to the gut. In addition, our results provide preliminary evidence for glucocorticoid modulation of plasma ghrelin levels.
Ghrelin in the Regulation of GH Secretion and Other Pituitary Hormones
Growth Hormone Related Diseases and Therapy, 2011
Ghrelin, a 28 amino acid octanoylated peptide predominantly produced by the stomach, was discovered to be the natural ligand of the type 1a growth hormone (GH) secretagogue receptor (GHS-R1a). Thus, it was considered as a natural GHS additional to growth hormone-releasing hormone (GHRH), although later on ghrelin has mostly been considered a major orexigenic factor. Ghrelin activity at the pituitary level is not fully specific for GH, because it also includes stimulatory effects on both the lactotroph and corticotroph system. In fact, ghrelin in humans significantly stimulates prolactin (PRL) secretion, independently of both gender and age and probably involving a direct action on somatomammotroph cells, and possesses an acute stimulatory effect on the activity of the hypothalamus-pituitary-adrenal axis, which is similar to that of the opioid antagonist naloxone, arginine-vasopressin (AVP) and even corticotropin-releasing hormone (CRH). Finally, ghrelin plays a relevant role in the modulation of the hypothalamus-pituitary-gonadal axis function, with a predominantly central nervous system (CNS)-mediated inhibitory effect upon the gonadotropin pulsatility both in animals and in humans.
Ghrelin and toxicity: recent findings and future challenges
Journal of Applied Toxicology, 2013
Ghrelin is a novel brain-gut peptide that plays various roles in mammals, including control of food intake and growth hormone release, as well as gastric motility and acid secretion in the gastrointestinal tract. It is mainly secreted by the gastric mucosa, but is also expressed in various other tissues. Different studies confirm the multiple biological roles of and possible protective effects of ghrelin. Multiple in vitro and in vivo studies support the powerful protective action of ghrelin against heart, gastric and liver injury. Moreover, ghrelin has been reported to be beneficial in renal tissue injury and excretory function after ischemia-reperfusion and to exert neuroprotective effects in cerebral ischemic regions. The aim of this review is to summarize and evaluate all the currently available in vivo and in vitro studies regarding the effects of ghrelin on tissue injury induced in different organs and tissues.
Saga of ghrelin: its structure, actions, and therapeutic uses
Asian Biomed, 2011
The fat-regulating hormones, adiponectin, ghrelin, and leptin have been studied extensively because therapeutic modality might be gleaned from their augmentation or blockade. Since a link between the hormone and control of hunger was found, ghrelin levels in the human body have received a great deal of attention over the past several years. This mini-review summarizes the role of ghrelin, describing its actions and therapeutic uses.
Novel analogs of ghrelin: physiological and clinical implications
European Journal of Endocrinology, 2004
Ghrelin, the 28 amino acid peptide recently identified as the natural ligand for the growth hormone (GH) secretagogue (GHS) receptor, has multiple activities in addition to stimulation of GH secretion, including stimulation of feeding and weight gain. To utilize these actions for potential therapeutic benefit, we have produced analogs of human ghrelin with enhanced metabolic stability, affinity for the GHS receptor, and efficacy in stimulating weight gain. We have also discovered an analog of ghrelin, BIM-28163, that is an antagonist at the GHS receptor and that fully inhibits GHS receptor activation induced by native ghrelin. In vivo, BIM-28163 does not increase GH secretion but fully blocks ghrelin-induced GH secretion. In contrast, BIM-28163 acts as a full agonist with regard to the ghrelin actions of stimulating weight gain and food intake. These results suggest that a receptor other than the GHS receptor mediates the actions of ghrelin on feeding and weight gain. This concept is strengthened by our observation that at certain hypothalamic sites, BIM-28163 acts as an antagonist of ghrelin-induced neuronal activation, while at other sites, both ghrelin and BIM-28163 induce neuronal activation via the same receptor. Collectively, these results indicate the existence of a novel ghrelin receptor that may regulate the feeding activity of ghrelin. Using BIM-28163 as a tool to define the endogenous role of ghrelin in normal GH secretion, we have demonstrated that antagonism of the GHS receptor in normal rats does not impair the pulsatility of GH secretion but lowers the pulse amplitude and mean GH level. These results demonstrate that endogenous ghrelin acts to amplify the basic pattern of GH secretion established by the interplay of hypothalamic GH-releasing hormone and somatostatin. These studies demonstrate the feasibility of creating ghrelin analogs that are selective for specific activities, as well as their utility in dissecting the role of ghrelin in both normal physiology and specific pathologies.
FEBS letters, 2003
The recent discovery of ghrelin, the endogenous ligand for the growth hormone secretagogue receptor, is the result of almost 25 years of research by many groups all around the world, and represents a milestone in our understanding of growth hormone secretion and energy homeostasis. This minireview is focused on recent studies on ghrelin, pointing out the cellular and molecular mechanisms involved in the gene expression of ghrelin since recent studies have unequivocally shown that ghrelin biological activity is dependent on a peculiar posttranslational processing. Major interest in this peptide derived from the fact that, in addition to other e¡ects, it is involved in the regulation of energy balance by inducing weight gain and reducing fat utilization. These activities are likely mediated by a CNS network of cells that is also modulated by other hormones such as leptin. Ghrelin has emerged as a premeal initiation factor that informs CNS about the status of the energy balance. The development of ghrelin analogs, agonists and antagonists, appears as a suitable approach for possible therapeutic intervention in a variety of disease states linked to alterations in body weight homeostasis. ß