scholarly journals Ghrelin receptors in rat and human nodose ganglia: putative role in regulating CB-1 and MCH receptor abundance

2006 ◽  
Vol 290 (6) ◽  
pp. G1289-G1297 ◽  
Author(s):  
Galina Burdyga ◽  
Andrea Varro ◽  
Rod Dimaline ◽  
David G. Thompson ◽  
Graham J. Dockray
Keyword(s):  
Receptor Expression ◽  
Afferent Neurons ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Nodose Ganglia ◽  
Melanin Concentrating Hormone ◽  
Ghrelin Receptors ◽  
Vagal Afferent ◽  
Immunohistochemical Studies

Intact vagal afferent neurons are required for the satiety effects of the intestinal hormone cholecystokinin (CCK) and the orexigenic effects of the gastric regulatory peptide ghrelin. In this study, we examined the localization of ghrelin receptors in nodose ganglia and their function in regulating the expression of other orexigenic receptors, notably cannabinoid (CB)-1 and melanin-concentrating hormone (MCH)-1 receptors. With the use of RT-PCR, transcripts corresponding to both functional [growth hormone secretagogue receptor (GHS-R)1a] and truncated forms (GHS-R1b) of the ghrelin receptor were detected in rat nodose ganglia. There was no difference in expression between rats fed ad libitum or fasted for up to 48 h. Immunohistochemical studies using antibodies directed at GHS-R1a revealed expression in over 75% of neurons also expressing CCK-1 receptors in the mid- and caudal regions of the ganglion. There was also expression in human nodose ganglia. In fasted rats in which CB-1 and MCH-1 receptor expression was increased, administration of ghrelin prevented the downregulation by refeeding. We conclude that the actions of CCK and ghrelin are mediated by a common population of vagal afferent neurons. Ghrelin may act to limit the action of CCK in depressing expression of CB-1 and MCH-1 receptors and other receptors.

scholarly journals Expression of cannabinoid CB1 receptors by vagal afferent neurons: kinetics and role in influencing neurochemical phenotype

2010 ◽  
Vol 299 (1) ◽  
pp. G63-G69 ◽  
Author(s):  
Galina Burdyga ◽  
Andrea Varro ◽  
Rod Dimaline ◽  
David G. Thompson ◽  
Graham J. Dockray
Keyword(s):  
Receptor Expression ◽  
Cb1 Receptors ◽  
Afferent Neurons ◽  
Y2 Receptor ◽  
Melanin Concentrating Hormone ◽  
Cb1 Antagonist ◽  
Vagal Afferent ◽  
G Protein Coupled ◽  
Stimulation Of

The intestinal hormone cholecystokinin (CCK) inhibits food intake via stimulation of vagal afferent neurons (VAN). Recent studies suggest that CCK also regulates the expression of some G protein-coupled receptors and neuropeptide transmitters in these neurons. The aim of the present study was to characterize the expression of cannabinoid (CB)1 receptors in VAN and to determine whether stimulation of these receptors plays a role in regulating neurochemical phenotype. Expression of CB1 in rat VAN was detectable by in situ hybridization or immunohistochemistry after 6 h of fasting and increased to a maximum after 24 h when ∼50% of neurons in the mid and caudal regions expressed the receptor. Melanin-concentrating hormone (MCH)1 receptors also increased with fasting, but the changes were delayed compared with CB1; in contrast Y2 receptors (Y2R) exhibited reciprocal changes in expression to CB1. Administration of CCK8s (10 nmol ip) to fasted rats decreased expression of CB1 with a t1/2 of ∼1 h compared with 3 h for MCH1. The action of CCK8s was inhibited by ghrelin and orexin-A. The CB1 agonist anandamide (intraperitoneally) reversed the effect of CCK8s on CB1, MCH1, and Y2 receptor expression. In contrast, in rats fasted for 18 h, administration of a CB1 antagonist/inverse agonist (AM281 ip) downregulated CB1 expression and increased Y2 receptor expression. Activation of vagal CB1 receptors therefore influences the neurochemical phenotype of these neurons, indicating a new and hitherto unrecognized role for endocannabinoids in gut-brain signaling.

scholarly journals Ghrelin and Growth Hormone Secretagogue Receptor Expression in Mice during Aging

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1323-1329 ◽  
Author(s):  
Yuxiang Sun ◽  
Jose Manuel Garcia ◽  
Roy G. Smith
Keyword(s):  
Pituitary Gland ◽  
Receptor Expression ◽  
Elderly Subjects ◽  
Mrna Levels ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Igf I ◽  
The Impact ◽  
The Brain

In well-nourished humans, GH and IGF-I decline during aging, and the responsiveness of the GH axis to exogenous ghrelin is attenuated with age. Intriguingly, the GH/IGF-I axis is rejuvenated by chronic treatment with the ghrelin mimetic MK-0677, resulting in improvements in body composition, suggesting that frail elderly subjects might benefit from treatment with ghrelin and ghrelin mimetics. Mouse models are widely used to study the effects of ghrelin, but the impact of age on the ghrelin pathway is unclear. In this study, total and active ghrelin peptides were measured in plasma, and ghrelin mRNA was quantitated in brain tissue from different aged C57BL/6J mice. Surprisingly, plasma levels of ghrelin peptide slightly increased with age; ghrelin mRNA levels were similar in brains from mice aged 2, 6, 12, and 28 months but higher in mice aged 18 and 24 months. The tissue distribution of Ghsr1a mRNA (ghrelin receptor) was also characterized, and pituitary and brain exhibited the highest levels of expression. In the pituitary gland, the highest concentration of Ghsr1a mRNA was observed at age 1–2 months, it was lower at 6 months, and remained unchanged for up to 30 months of age. This result is consistent with the finding that GH release in response to exogenous ghrelin was not significantly different in mice aged 7–30 months. In the brain, Ghsr1a mRNA levels remained stable during aging. Hence, in C57BL/6J male mice, aging is not associated with changes in circulating ghrelin levels or changes in ghrelin receptor expression in the pituitary gland and brain.

Ghrelin counteracts insulin-induced activation of vagal afferent neurons via growth hormone secretagogue receptor

Neuropeptides ◽  
2015 ◽  
Vol 52 ◽  
pp. 55-60 ◽  
Author(s):  
Yusaku Iwasaki ◽  
Katsuya Dezaki ◽  
Parmila Kumari ◽  
Masafumi Kakei ◽  
Toshihiko Yada
Keyword(s):  
Growth Hormone ◽  
Afferent Neurons ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Vagal Afferent

scholarly journals Functional interaction between Ghrelin and GLP-1 regulates feeding through the vagal afferent system

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Weidong Zhang ◽  
T. M. Zaved Waise ◽  
Koji Toshinai ◽  
Wakaba Tsuchimochi ◽  
Farhana Naznin ◽  
...  
Keyword(s):  
Vagal Afferents ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Electrophysiological Properties ◽  
Feeding Regulation ◽  
Nodose Ganglia ◽  
Patch Clamp Experiment ◽  
Fine Control ◽  
Vagal Afferent ◽  
Glucagon Like Peptide 1

Abstract The gastrointestinal tract transmits feeding-regulatory signals to the brain via neuronal and hormonal pathways. Here we studied the interaction between the orexigenic gastric peptide, ghrelin, and the anorectic intestinal peptide, glucagon-like peptide 1 (GLP-1), in terms of feeding regulation via the vagal afferents. GLP-1 preadministration 30 min before ghrelin administration to rats and mice abolished ghrelin-induced food intake, while ghrelin preadministration abolished the anorectic effect of GLP-1. Ghrelin preadministration suppressed GLP-1-induced Fos expression in the nodose ganglia (NG). Electrophysiological assessment confirmed that the initially administered peptide abolished the vagal afferent electrical alteration induced by the subsequently administered peptide. Both the growth hormone secretagogue receptor (GHSR) and the GLP-1 receptor (GLP-1R) are co-localised in a major proportion of NG neurons that innervate the stomach. In these Ghsr+Glp1r+ neurons, ghrelin preadministration abolished the GLP-1-induced calcium response. Ghrelin generated a hyperpolarising current and GLP-1 generated a depolarising current in isolated NG neurons in a patch-clamp experiment. Ghrelin and GLP-1 potently influenced each other in terms of vagally mediated feeding regulation. This peptidergic interaction allows for fine control of the electrophysiological properties of NG neurons.

scholarly journals Cannabinoid-Induced Conditioned Place Preference, Intravenous Self-Administration, and Behavioral Stimulation Influenced by Ghrelin Receptor Antagonism in Rats

2021 ◽  
Vol 22 (5) ◽  
pp. 2397
Author(s):  
Chrysostomos Charalambous ◽  
Tereza Havlickova ◽  
Marek Lapka ◽  
Nina Puskina ◽  
Romana Šlamberová ◽  
...  
Keyword(s):  
Conditioned Place Preference ◽  
Fixed Ratio ◽  
Place Preference ◽  
Self Administration ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Addiction Therapy ◽  
Significant Efficacy ◽  
Lever Pressing

Cannabis/cannabinoids are widely used for recreational and therapy purposes, but their risks are largely disregarded. However, cannabinoid-associated use disorders and dependence are alarmingly increasing and an effective treatment is lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in cannabinoid abuse remains unclear. Therefore, the aim of our study was to investigate whether the GHS-R1A antagonist JMV2959 could reduce the tetrahydrocannabinol (THC)-induced conditioned place preference (CPP) and behavioral stimulation, the WIN55,212-2 intravenous self-administration (IVSA), and the tendency to relapse. Following an ongoing WIN55,212-2 self-administration, JMV2959 3 mg/kg was administered intraperitoneally 20 min before three consequent daily 120-min IVSA sessions under a fixed ratio FR1, which significantly reduced the number of the active lever-pressing, the number of infusions, and the cannabinoid intake. Pretreatment with JMV2959 suggested reduction of the WIN55,212-2-seeking/relapse-like behavior tested in rats on the twelfth day of the forced abstinence period. On the contrary, pretreatment with ghrelin significantly increased the cannabinoid IVSA as well as enhanced the relapse-like behavior. Co-administration of ghrelin with JMV2959 abolished/reduced the significant efficacy of the GHS-R1A antagonist in the cannabinoid IVSA. Pretreatment with JMV2959 significantly and dose-dependently reduced the manifestation of THC-induced CPP. The THC-CPP development was reduced after the simultaneous administration of JMV2959 with THC during conditioning. JMV2959 also significantly reduced the THC-induced behavioral stimulation in the LABORAS cage. Our findings suggest that GHS-R1A importantly participates in the rewarding/reinforcing effects of cannabinoids.

scholarly journals Cortistatin Is Not a Somatostatin Analogue but Stimulates Prolactin Release and Inhibits GH and ACTH in a Gender-Dependent Fashion: Potential Role of Ghrelin

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4800-4812 ◽  
Author(s):  
José Córdoba-Chacón ◽  
Manuel D. Gahete ◽  
Ana I. Pozo-Salas ◽  
Antonio J. Martínez-Fuentes ◽  
Luis de Lecea ◽  
...  
Keyword(s):  
Metabolic Phenotype ◽  
Somatostatin Analogue ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ancestral Gene ◽  
Ghrelin Receptor ◽  
Physiological Relevance

Cortistatin (CST) and somatostatin (SST) evolve from a common ancestral gene and share remarkable structural, pharmacological, and functional homologies. Although CST has been considered as a natural SST-analogue acting through their shared receptors (SST receptors 1–5), emerging evidence indicates that these peptides might in fact exert unique roles via selective receptors [e.g. CST, not SST, binds ghrelin receptor growth hormone secretagogue receptor type 1a (GHS-R1a)]. To determine whether the role of endogenous CST is different from SST, we characterized the endocrine-metabolic phenotype of male/female CST null mice (cort−/−) at hypothalamic-pituitary-systemic (pancreas-stomach-adrenal-liver) levels. Also, CST effects on hormone expression/secretion were evaluated in primary pituitary cell cultures from male/female mice and female primates (baboons). Specifically, CST exerted an unexpected stimulatory role on prolactin (PRL) secretion, because both male/female cort−/− mice had reduced PRL levels, and CST treatment (in vivo and in vitro) increased PRL secretion, which could be blocked by a GHS-R1a antagonist in vitro and likely relates to the decreased success of female cort−/− in first-litter pup care at weaning. In contrast, CST inhibited GH and adrenocorticotropin-hormone axes in a gender-dependent fashion. In addition, a rise in acylated ghrelin levels was observed in female cort−/− mice, which were associated with an increase in stomach ghrelin/ghrelin O-acyl transferase expression. Finally, CST deficit uncovered a gender-dependent role of this peptide in the regulation of glucose-insulin homeostasis, because male, but not female, cort−/− mice developed insulin resistance. The fact that these actions are not mimicked by SST and are strongly gender dependent offers new grounds to investigate the hitherto underestimated physiological relevance of CST in the regulation of physiological/metabolic processes.

scholarly journals Ghrelin Amplifies Dopamine Signaling by Cross Talk Involving Formation of Growth Hormone Secretagogue Receptor/Dopamine Receptor Subtype 1 Heterodimers

2006 ◽  
Vol 20 (8) ◽  
pp. 1772-1785 ◽  
Author(s):  
Hong Jiang ◽  
Lorena Betancourt ◽  
Roy G. Smith
Keyword(s):  
Dopamine Receptor ◽  
Fluorescent Protein ◽  
Green Fluorescent Protein Fluorescence ◽  
Receptor Subtype ◽  
Protein Fluorescence ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Dopamine Signaling

Abstract Our objective is to determine the neuromodulatory role of ghrelin in the brain. To identify neurons that express the ghrelin receptor [GH secretagogue receptor (GHS-R)], we generated GHS-R-IRES-tauGFP mice by gene targeting. Neurons expressing the GHS-R exhibit green fluorescence and are clearly evident in the hypothalamus, hippocampus, cortex, and midbrain. Using immunohistochemistry in combination with green fluorescent protein fluorescence, we identified neurons that coexpress the dopamine receptor subtype 1 (D1R) and GHS-R. The potential physiological relevance of coexpression of these two receptors and the direct effect of ghrelin on dopamine signaling was investigated in vitro. Activation of GHS-R by ghrelin amplifies dopamine/D1R-induced cAMP accumulation. Intriguingly, amplification involves a switch in G protein coupling of the GHS-R from Gα11/q to Gαi/o by a mechanism consistent with agonist-dependent formation of GHS-R/D1R heterodimers. Most importantly, these results indicate that ghrelin has the potential to amplify dopamine signaling selectively in neurons that coexpress D1R and GHS-R.

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