Disease relevance of Ghsr

• We previously created transgenic (Tg) rats whose GHS-R expression is reduced in the Arc, showing lower body weight and shorter nose-tail length [1].
• Upregulation of cardiovascular ghrelin receptor occurs in the hyperdynamic phase of sepsis [2].
• Such potent GH-inhibitory chimeric peptides may be of potential importance in the therapy of acromegaly, as well as provide novel tools to study the regulation of GH secretion by GHRP and somatostatin [3].
• Hexarelin, a synthetic hexapeptide of the growth hormone-releasing peptide (GHRP) family with strong growth hormone (GH)-releasing activity, features protecting activity against postischemic ventricular dysfunction in hearts from GH-deficient and senescent rats [4].
• We have previously reported that a 7-d pretreatment with hexarelin, a synthetic ligand of the GH secretagogue receptor (GHS-R), largely prevented damages induced by ischemia and reperfusion in isolated rat hearts [5].

Psychiatry related information on Ghsr

• Injection of GHS-R antagonist blocked the fasted motor activity in both the stomach and duodenum in vagotomized rats but did not affect the fasted motor activity in normal rats [6].

High impact information on Ghsr

• A binding study on the vagus nerve by (125)I-ghrelin was performed to determine the transport of the ghrelin receptor from vagus afferent neurons to the periphery [7].
• The presence of the ghrelin receptor in vagal afferent neurons was assessed by using reverse-transcription polymerase chain reaction and in situ hybridization histochemistry [7].
• These results show that the level of GHS-R expression in the ARC is reduced by leptin and increased by ghrelin and that the effect of ghrelin may be GH dependent [8].
• Expression of the rat GHS-R was observed specifically in the pituitary and hypothalamus when compared with control tissues [9].
• The recent cloning of the GHS-R from human and swine pituitary gland identifies yet a third G protein-coupled receptor (GPC-R) involved in the control of GH release and further supports the existence of an undiscovered hormone that may activate this receptor [9].

Chemical compound and disease context of Ghsr

• GHRP also decreased myocardial creatine kinase release in hypophysectomized rats subjected to acute myocardial ischemia [10].

Biological context of Ghsr

• A full-length contiguous cDNA from rat hypothalamus was isolated and shown to be identical in its nucleotide and deduced amino acid sequence to the rat pituitary GHS-R [9].
• A single intron of approximately 2 kb divides the open reading frame into two exons encoding TM 1-5 and TM 6-7, thus placing the GHS-R into the intron-containing class of GPC-Rs [9].
• In addition, determination of the nucleotide sequence for the human GHS-R gene confirmed the position of an intron in the human GHS-R gene at this position [9].
• Hypothalamic GHS-R mRNA levels increased with age but exhibited no significant sex difference at each age tested [11].
• These results suggest that GHRH-R is vital for GHRH-induced GH secretion but only partially involved in GHRP-2-stimulated GH secretion under the condition of down-regulation of GHS-R gene transcription [12].

Anatomical context of Ghsr

• GHS-R mRNA is prominently expressed in arcuate (ARC) and ventromedial nuclei (VMN) and in hippocampus, but not in the periventricular nucleus [13].
• In conclusion, the expression of GHS-R in rat adipocytes increases with the age and during adipogenesis [14].
• The levels of GHS-R mRNA increased by up to 4-fold in adipose tissue from epididymal and parametrial regions as the rat aged from 4-20 wk and were significantly elevated during the differentiation of preadipocytes in vitro [14].
• In addition, cellular distribution of GHS-R within adult testis tissue was assessed [15].
• Reverse transcription-polymerase chain reaction demonstrated the expression of ghrelin and GHS-R in the rat adrenal cortex, and high adrenal concentrations of immunoreactive ghrelin were detected by radioimmune assay (RIA) [16].

Associations of Ghsr with chemical compounds

• In addition, GH-releasing peptides, such as GHRP-6 and the nonpeptide mimetics, L-692,429 and MK-0677, stimulate GH release through their activation of a distinct receptor, the GH secretagogue receptor (GHS-R) [9].
• Taken together, these data demonstrate that changes in the levels of pituitary GHS-R mRNA, but not GHRH-R mRNA, are associated with changes in the gonadal steroid environment, thereby implicating the GHS/GHS-R signalling system as a control point in the establishment and maintenance of sexually dimorphic patterns of GH secretion [11].
• In the present study, the effect of i.c.v. injection of different ghrelins including chicken and bullfrog ghrelin, and synthetic GH-releasing peptide (GHRP) on feeding of neonatal chicks was investigated [17].
• Although the actions of dermorphin, 2549, and GHRP on GH release are GHRH dependent, release of endogenous GHRH does not explain how GH is released synergistically by the combination of these peptides [18].
• Hexarelin modulates the expression of growth hormone secretagogue receptor type 1a mRNA at hypothalamic and pituitary sites [19].

Regulatory relationships of Ghsr

• We performed dual chromogenic and autoradiographic in situ hybridization to test the hypothesis that GHRH neurons in the hypothalamus coexpress GHS-R mRNA [20].
• In the arcuate nucleus, GHS-R mRNA was expressed in 94 +/- 1% of the neurons expressing NPY, 8 +/- 2% of those expressing POMC and 30 +/- 6% expressing SRIH mRNA [21].
• Thus, the present studies indicate that IGF-I could inhibit GH secretion at least in part by regulating the expression of the GHS-R [22].
• METHODS: Leptin-receptor mutated Zucker diabetic fatty (ZDF) and lean control rats were treated with the ghrelin-receptor ligand, tabimorelin (50 mg/kg p.o.) for 18 days, and the effects on body weight, food intake and body composition were investigated [23].
• Ghrelin receptor agonist GHRP-2 prevents arthritis-induced increase in E3 ubiquitin-ligating enzymes MuRF1 and MAFbx gene expression in skeletal muscle [24].

Other interactions of Ghsr

• GH secretagogue (GHS)/ghrelin stimulates GH secretion by binding mainly to its receptor (GHS-R) on GHRH neurons in the arcuate nucleus (Arc) of the hypothalamus [1].
• GHRH-R mRNA levels were comparable in males and females within each age while GHS-R mRNA levels were gender dependent [11].
• These results indicate that the chicken GHS receptor is affected by several forms of GHS, and that food intake of neonatal chicks is inhibited by GHS receptor agonists [17].
• Taken together, these results indicate that GHRH-induced up-regulation of pituitary GHS-R synthesis in vivo is indirect and independent of both somatostatin and GH [25].
• Stimulation of the arcuate NPY neurons via GHS-R may explain the increased appetite and the cortisol release seen after administration of some GHS compounds [21].

Analytical, diagnostic and therapeutic context of Ghsr

• We demonstrate that our lead compound, L-NOX-B11, binds ghrelin with low-nanomolar affinity and inhibits ghrelin-mediated GHS-receptor activation in cell culture with an IC(50) of 5 nM. l-NOX-B11 is highly specific for the bioactive, n-octanoylated form of ghrelin [26].
• Serum was analyzed for GH, pituitaries were collected, and GHS-R and GHRH receptor (GHRH-R) messenger RNA (mRNA) levels were determined by RT-PCR [25].
• Accordingly, we examined the effects of GHRP and PACAP on GH secretion at the single cell level using the reverse hemolytic plaque assay which allows distinction of effects on the number of secreting cells and the amount of hormone each cell secretes [27].
• The calcium response of cardiocytes to GHRP was visualized using confocal microscopy [28].
• At these times, the mean log pituitary GHS-R mRNA contents were significantly lower in the GC rat group than in the control group [29].

References