The Effects of Centrally Administered Apelin-13 on Food Intake, Water Intake and Pituitary Hormone Release in Rats

doi:10.1006/bbrc.2002.6575

Biochemical and Biophysical Research Communications

Volume 291, Issue 5, 15 March 2002, Pages 1208-1212

https://doi.org/10.1006/bbrc.2002.6575 Get rights and content

Abstract

Apelin is the recently identified endogenous ligand for the G-protein-coupled receptor, APJ. Preproapelin and APJ mRNA are found in hypothalamic regions known to be important in the regulation of food and water intake, and pituitary hormone release. The effects of intracerebroventricular (ICV) administration of pyroglutamylated apelin-13 on food and water intake and pituitary hormone release in rats were investigated. Apelin-13 had little effect on food intake, but dose-dependently increased drinking behaviour and water intake at 1 h. Apelin-13 (10 nmol) increased water intake by up to sixfold compared to saline. Compared to saline control, apelin-13 (10 nmol) significantly increased plasma ACTH and corticosterone and decreased plasma prolactin, LH and FSH at 30 min. In vitro, apelin-13 stimulated the release of CRH and AVP from hypothalamic explants, but had no effect on NPY release. These results suggest that apelin may play an important role in the hypothalamic regulation of water intake and endocrine axes.

References (15)

B.F O'Dowd et al.
A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11
Gene
(1993)
K Tatemoto et al.
Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor
Biochem. Biophys. Res. Commun.
(1998)
M Hosoya et al.
Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin
J. Biol. Chem.
(2000)
Y Kawamata et al.
Molecular properties of apelin: Tissue distribution and receptor binding
Biochim. Biophys. Acta
(2001)
A.M O'Carroll et al.
Distribution of mRNA encoding B78/apj, the rat homologue of the human APJ receptor, and its endogenous ligand apelin in brain and peripheral tissues
Biochim. Biophys. Acta
(2000)
D Sunter et al.
Orexins: Effects on behavior and localisation of orexin receptor 2 messenger ribonucleic acid in the rat brainstem
Brain Res.
(2001)
S.A Stanley et al.
Actions of cocaine- and amphetamine-regulated transcript (CART) peptide on regulation of appetite and hypothalamo-pituitary axes in vitro and in vivo in male rats
Brain Res.
(2001)

There are more references available in the full text version of this article.

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The regulatory effects of the apelin/APJ system on depression: A prospective therapeutic target
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Depression is a debilitating neuropsychological disorder characterized by high incidence, high recurrence, high suicide, and high disability rates, which poses serious threats to human health and imposes heavy psychological and economic burdens on family and society. The pathogenesis of depression is extremely complex, and its etiology is multifactorial. Mounting evidence suggests that apelin and apelin receptor APJ, which compose the apelin/APJ system, are related to the development of depression. However, the specific mechanism is still unclear, and research in this area in human is still insufficient. Acceleration of research into the regulatory effects and underlying mechanisms of the apelin/APJ system in depression may identify attractive therapeutic targets and contribute to the development of novel intervention strategies against this devastating psychological disorder. In this review, we mainly discuss the regulatory effects of apelin/APJ system on depression and its potential therapeutic applications.
Hypophagia induced by intracerebroventricular injection of apelin-13 is mediated via CRF1/CRF2 and MC3/MC4 receptors in neonatal broiler chicken
2023, Behavioural Brain Research
Previous studies have shown the role of apelin and its receptors in the regulation of food intake. In the present study, we investigate the mediating role of melanocortin, corticotropin, and neuropeptide Y systems in apelin-13- induced food intake in broilers. Eight trials were run in the current investigation to ascertain the relationships between the aforementioned systems and apelin-13 on food intake and behavioral changes after apelin-13 administration. In experiment 1, hens were given an intracerebroventricular administration of a solution for control in addition to apelin-13 (0.25, 0.5, and 1 µg). Astressin-B (a CRF1/CRF2 receptor antagonist, 30 µg), apelin-13 (1 µg), and administration of astressin-B and apelin-13 concurrently, were all injected into the birds in experiment 2. Experiments 3 through 8 were quite similar to experiment 2, with the exception of astressin2-B (CRF2 receptor antagonist, 30 µg), SHU9119 (MC3/MC4 receptor antagonist, 0.5 nmol), MCL0020 (MC4 receptor antagonist, 0.5 nmol), BIBP-3226 (NPY1 receptor antagonist, 1.25 nmol), BIIE 0246 (NPY2 receptor antagonist, 1.25 nmol), and CGP71683A (NPY5 receptor antagonist, 1.25 nmol) were injected instead of astressin-B. After then, total food consumption was monitored for 6 h. Apelin-13 injections of 0.5 and 1 µg decreased feeding (P < 0.05). The hypophagic effects of apelin were attenuated following the simultaneous administration of Astressin-B and Astressin2-B with apelin-13 (P > 0.05). Co-infusion of SHU9119 and apelin-13 reduced the appetite-decreasing effects of apelin-13 (P > 0.05). When MCL0020 and apelin-13 were injected at the same time, the hypophagia that apelin-13 induced was eliminated (P > 0.05). BIBP-3226, BIIE 0246, and CGP71683A had no effect on the hypophagia brought on by apelin-13 (P > 0.05). Also, apelin-13 significantly increased number of steps, jumps, exploratory food, pecks and standing time while decreased siting time (P < 0.05). These findings suggest that apelin-13-induced hypophagia in hens may involve the CRF1/CRF2 and MC3/MC4 receptors.
Several neuropeptides involved in parkinsonian neuroprotection modulate the firing properties of nigral dopaminergic neurons
2023, Neuropeptides
Parkinson's disease is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. The surviving nigral dopaminergic neurons display altered spontaneous firing activity in Parkinson's disease. The firing rate of nigral dopaminergic neurons decreases long before complete neuronal death and the appearance of parkinsonian symptoms. A mild stimulation could rescue dopaminergic neurons from death and in turn play neuroprotective effects. Several neuropeptides, including cholecystokinin (CCK), ghrelin, neurotensin, orexin, tachykinins and apelin, within the substantia nigra pars compacta play important roles in the modulation of spontaneous firing activity of dopaminergic neurons and therefore involve motor control and motor disorders. Here, we review neuropeptide-induced modulation of the firing properties of nigral dopaminergic neurons. This review may provide a background to guide further investigations into the involvement of neuropeptides in movement control by modulating firing activity of nigral dopaminergic neurons in Parkinson's disease.
Expression and localization of apelin and apelin receptor (APJ) in buffalo ovarian follicles and corpus luteum and the in-vitro effect of apelin on steroidogenesis and survival of granulosa cells
2023, Theriogenology
Apelin is an adipose tissue-derived hormone with many physiological functions, including the regulation of female reproduction. It acts through an orphan G protein-coupled receptor APJ/APLNR. The present study aimed to investigate the expression of apelin and its receptor APJ in the ovarian follicles and corpus luteum (CL) and the role of apelin on steroidogenesis and cell survival. Ovarian follicles were classified into four groups based on size and estradiol (E₂) level in the follicular fluid as follows: (i) F1 (4–6 mm; <0.5 ng/mL) (ii) F2 (7–9 mm; 0.5–5 ng/mL) (iii) F3 (10–13 mm; 5–40 ng/mL) and (iv) F4 (dominant/pre-ovulatory follicle) (>13 mm; >180 ng/mL). The corpora lutea (CL) were categorized into early (CL1), mid (CL2), late luteal (CL3), and regressing (CL4) CL stages. Expression of apelin increased with follicle size, with significantly greatest in the dominant or pre-ovulatory follicle (P < 0.05). Expression of APJ was greater in large and dominant follicles than in small and medium follicles (P < 0.05). In CL, the mRNA and protein abundance of apelin and apelin receptor was greater during mid (CL2) and late luteal (CL3) stages as compared to early (CL1) and regressing (CL4) stages (P < 0.05). Both the factors were localized in granulosa and theca cells of follicles and small and large luteal cells of CL. The pattern of the intensity of immunofluorescence was similar to mRNA and protein expression. Granulosa cells were cultured in vitro and treated at 1, 10, and 10 ng/mL apelin-13 either alone or in the presence of the follicle-stimulating hormone (FSH) (30 ng/mL) or insulin-like growth factor-I (IGF-I) (10 ng/mL) for 48 h. The luteal cells were treated with apelin-13 at 1, 10, and 100 ng/mL doses for 48 h. Apelin treatment at 10 and 100 ng/ml significantly (P < 0.05) increased E₂ secretion, cytochrome P450 aromatase or CYP19A1 expression in GC. In luteal cells, apelin at 10 ng/mL and 100 ng/mL significantly (P < 0.05) increased progesterone (P₄) secretion and HSD3B1 expression. In GCs, apelin, either alone or in combination, increased PCNA expression and inhibited CASPASE3 expression suggesting its role in cell survival. In conclusion, this study provides novel evidence for the presence of apelin and receptor APJ in ovarian follicles and corpora lutea and the stimulatory effect on E₂ and P₄ production and promotes GC survival in buffalo, suggesting the role of apelin in follicular and luteal functions in buffalo.
Neuropeptide apelin presented in the dopaminergic neurons modulates the neuronal excitability in the substantia nigra pars compacta
2022, Neuropharmacology
The dopaminergic neurons in the substantia nigra pars compacta are characterized by autonomous pacemaking activity. The spontaneous firing activity of nigral dopaminergic neurons plays an important role in physiological function and is essential for their survival. Importantly, the spontaneous firing activity may also be involved in the preferential vulnerability of the nigral dopaminergic neurons in Parkinson's disease (PD). The neuropeptide apelin was reported to exert neuroprotective effects in neurodegenerative diseases, including PD. And it was noticed that apelin modulates neuronal activity in some brain regions. The present study investigated the electrophysiological and behavioral effects of apelin in the substantia nigra. Double-labeling immunofluorescence showed that apelin was present in nigral dopaminergic neurons and that these neurons expressed apelin receptor APJ. Further single unit in vivo electrophysiological recordings revealed that endogenous apelin tonically increased the firing rate of nigral dopaminergic neurons in both normal and parkinsonian animals. Exogenous apelin-13 exerted excitatory effects on the majority of nigral dopaminergic neurons, yet reduced excitability in a subset of neurons. In addition, nigral application of apelin-13 increased motor activity in normal rats and blocking endogenous apelin reduced motor activity. Considering the involvement of the spontaneous firing activity of nigral dopaminergic neurons in the development of PD and the possibility that apelin acts in an autocrine manner on apelin receptors expressed by nigral dopaminergic neurons, the modulation of the spontaneous firing activity of nigral dopaminergic neurons by apelin may serve as a neuroprotective factor in PD.
How does apelin affect LH levels? An investigation at the level of GnRH and KNDy neurons
2022, Molecular and Cellular Endocrinology
Hypothalamic control of reproduction relies on GnRH and kisspeptin (KP) secretions. KP neurons are sensitive to sex steroids and metabolic status and their distribution overlaps with neurons producing apelin, a metabolic hormone known to decrease LH secretion in rats. Here, we observed neuroanatomical contacts between apelin fibers and both KP and GnRH neurons in the hypothalamus of male rodents. Intracerebroventricular apelin infusion for 2 weeks in male mice did not decrease LH levels nor did it affect gene expression for KP, neurokinin B and dynorphin. Finally, increasing apelin concentrations did not modulate Ca²⁺ levels of cultured GnRH neurons, while 10 μM apelin infusion on forskolin pretreated GnRH neurons revoked a rhythmic activity in 18% of GnRH neurons. These results suggest that acute apelin effect on LH secretion does not involve modulation of gene expression in KP neurons but may affect the secretory activity of GnRH neurons.

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¹: To whom correspondence and reprint requests should be addressed at Endocrine Unit, 6th Floor, Commonwealth Building, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. Fax: 0208 383 3142. E-mail: [email protected].

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Biochemical and Biophysical Research Communications

Abstract

References (15)

A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11

Gene

Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor

Biochem. Biophys. Res. Commun.

Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin

J. Biol. Chem.

Molecular properties of apelin: Tissue distribution and receptor binding

Biochim. Biophys. Acta

Distribution of mRNA encoding B78/apj, the rat homologue of the human APJ receptor, and its endogenous ligand apelin in brain and peripheral tissues

Biochim. Biophys. Acta

Orexins: Effects on behavior and localisation of orexin receptor 2 messenger ribonucleic acid in the rat brainstem

Brain Res.

Actions of cocaine- and amphetamine-regulated transcript (CART) peptide on regulation of appetite and hypothalamo-pituitary axes in vitro and in vivo in male rats

Brain Res.

Cited by (287)

The regulatory effects of the apelin/APJ system on depression: A prospective therapeutic target

Hypophagia induced by intracerebroventricular injection of apelin-13 is mediated via CRF1/CRF2 and MC3/MC4 receptors in neonatal broiler chicken

Several neuropeptides involved in parkinsonian neuroprotection modulate the firing properties of nigral dopaminergic neurons

Expression and localization of apelin and apelin receptor (APJ) in buffalo ovarian follicles and corpus luteum and the in-vitro effect of apelin on steroidogenesis and survival of granulosa cells

Neuropeptide apelin presented in the dopaminergic neurons modulates the neuronal excitability in the substantia nigra pars compacta

How does apelin affect LH levels? An investigation at the level of GnRH and KNDy neurons

Regular ArticleThe Effects of Centrally Administered Apelin-13 on Food Intake, Water Intake and Pituitary Hormone Release in Rats

Abstract

Gene

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Brain Res.

Brain Res.

Regular Article
The Effects of Centrally Administered Apelin-13 on Food Intake, Water Intake and Pituitary Hormone Release in Rats