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Apelin Receptor Antagonist
Apelin-13 (F13A) (Huamn, Bovine), replcement of Phe with Ala at C-terminal
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Figure 1. Apelin-36 Antibody Immunoblot
Analyses. Immunoblot analysis of whole cell lysates using the apelin-36
antibody (from Phoenix Pharmaceuticals).
(A) Shown are samples from COS-7 cells expressing rat preproapelin
(lane 1) and heart tissue samples for a control mouse (lane 2) and
a preproapelin-transgenic littermate (lane 3). (B) Samples from
COS-7 cells expressing rat preproapelin either untreated (lane 1)
or treated with 50 mM DTT and 100 mM IAA for 30 min at 60 °C
(lane 2). For all lanes, 25 µg of protein was used. The immunoblots
shown are representative of two independent experiments. Lee DK, et al. Endocrinology. 2004 Oct 14 [Epub ahead of print] |
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Figure 2. Effects of apelin peptides on mean
arterial blood pressure in anaesthetized rats. (A) Time-course changes
in MABP (% basal) after i.v. administration of 15 µg/kg apelin-12
or apelin-13 into Wistar or SHR at time=0 (arrow). Included is a
representative time-course in heart rate (% basal) after i.v. administration
of 15 µg/kg apelin-13 into SHR (open circles), as plotted
vs. the right y-axis (Heart Rate). Data are mean ± SEM. (B)
Time-course changes in MABP (% basal) after i.v. administration
of 15 µg/kg apelin-13 analogues into SHR at time=0 (arrow).
Data are mean ± SEM. (C) Comparison of the maximum decrease
in MABP (% basal) of the apelin analogues in SHR. *P<0.0001 vs.
Apelin-13(F13A) treatment. Lee DK, et al. Endocrinology. 2004 Oct 14 [Epub ahead of print] |
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Figure 3. Apelin-13(F13A) is an Antagonist
for Apelin-13 In Vivo. (A) Time-course changes in systolic (open
squares) and diastolic (open triangles) blood pressure (mmHg) after
i.v. administration of 15 µg/kg apelin-13 (black arrow) and
30 µg/kg apelin 13(F13A) (open arrow) into SHR. Data are mean
± SEM (n = 3). (B) Dose response of apelin-13(F13A) i.v.
administration at 0.1 (n=3), 3 (n=4), 10 (n=5) and 30 (n=5) µg/kg
with a concomitant injection of apelin-13 (15 µg/kg) into
SHR. Shown is the MABP (% basal) at maximum decrease within 1 minute
post-injection. Data are mean ± SEM. (C) Comparison of the
increase in MABP (% over basal) after i.v. administration of angiotensin
II (40 ng/kg) alone or angiotensin II (40 ng/kg) and apelin-13(F13A)
(30 µg/kg) together. Data are mean ± SEM (n=5) with
no significant difference observed between the two treatments. Lee
DK, et al. Endocrinology. 2004 Oct 14 [Epub ahead of print] |
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Immunocytochemical localization of the endogenous vasoactive peptide apelin to human vascular and endocardial endothelial cells
Apelin, the proposed endogenous peptide ligand of the
novel G-protein-coupled receptor APJ, has been shown to possess potent
vasodilator and positive inotropic effects in rats and humans in vivo.
However, in humans, no endogenous source of apelin has been reported.
Therefore, based on the presence of APJ and mRNA encoding apelin in human
tissues, we investigated the expression of apelin in freshfrozen human
tissue from right atrium, left ventricle, lung, kidney, adrenal and large
conduit vessels using immunocytochemistry. Apelin-like immunoreactivity
(apelin-LI) was detected in vascular endothelial cells lining blood vessels
in the human heart, kidney, adrenal gland and lung and in endothelial
cells of large conduit vessels. Apelin-LI was also present in endocardial
endothelial cells lining recesses of the right atrium. Apelin-LI was not
present or below the level of detection in cardiomyocytes, Purkinje’s
cells, pulmonary or renal epithelial cells, secretory cells of the adrenal
gland, vascular smooth muscle cells, adipocytes, nerves and connective
tissue. The restricted presence of apelin- LI in endothelial cells suggests
that endothelial apelin may play a role as a locally secreted cardiovascular
mediator acting on APJ receptors present on the vascular smooth muscle
and on cardiac myocytes to regulate vascular tone and cardiac contractility.
Matthias J. Kleinz*, Anthony P. Davenport. Regulatory
Peptides 118 (2004) 119–125
Novel role for the potent endogenous inotrope apelin
in human cardiac dysfunction
BACKGROUND: Apelin is among the most potent stimulators of cardiac contractility
known. However, no physiological or pathological role for apelin-angiotensin
receptor-like 1 (APJ) signaling has ever been described. METHODS AND RESULTS:
We performed transcriptional profiling using a spotted cDNA microarray
with 12 814 unique clones on paired samples of left ventricle obtained
before and after placement of a left ventricular assist device in 11 patients.
The significance analysis of microarrays and a novel rank consistency
score designed to exploit the paired structure of the data confirmed that
natriuretic peptides were among the most significantly downregulated genes
after offloading. The most significantly upregulated gene was the G-protein-coupled
receptor APJ, the specific receptor for apelin. We demonstrate here using
immunoassay and immunohistochemical techniques that apelin is localized
primarily in the endothelium of the coronary arteries and is found at
a higher concentration in cardiac tissue after mechanical offloading.
These findings imply an important paracrine signaling pathway in the heart.
We additionally extend the clinical significance of this work by reporting
for the first time circulating human apelin levels and demonstrating increases
in the plasma level of apelin in patients with left ventricular dysfunction.
CONCLUSIONS: The apelin-APJ signaling pathway emerges as an important
novel mediator of cardiovascular control.
Chen MM, et al. Circulation. 2003 Sep 23;108(12):1432-9. Epub 2003 Sep
08
Circulating and cardiac levels of apelin, the novel ligand of the orphan
receptor APJ, in patients with heart failure
The orphan receptor APJ and its recently identified endogenous ligand,
apelin, are expressed in the heart. However, their importance in the human
cardiovascular system is not known. This study shows that apelin-like
immunoreactivity is abundantly present in healthy human heart and plasma.
Gel filtration HPLC analysis revealed that atrial and plasma levels of
high molecular weight apelin, possibly proapelin, were markedly higher
than those of mature apelin-36 itself. As assessed by quantitative RT-PCR
analysis, left ventricular apelin mRNA levels were increased 4.7-fold
in chronic heart failure (CHF) due to coronary heart disease (p<0.01)
and 3.3-fold due to idiopathic dilated cardiomyopathy (p<0.05), whereas
atrial apelin mRNA levels were unchanged. Atrial and plasma apelin-like
immunoreactivity (using Phoenix's Apelin-36 (Human) RIA Kit) as
well as atrial and ventricular APJ receptor mRNA levels were significantly
decreased in CHF. Our results suggest that a new cardiac regulatory peptide,
apelin, and APJ receptor may contribute to the pathophysiology of human
CHF.
Foldes G, et al. Biochem Biophys Res Commun. 2003 Aug 29;308(3):480-5
Apelin, the novel endogenous ligand of the orphan
receptor APJ, regulates cardiac contractility
The orphan receptor APJ and its recently identified endogenous ligand,
apelin, exhibit high levels of mRNA expression in the heart. However,
the functional importance of apelin in the cardiovascular system is not
known. In isolated perfused rat hearts, infusion of apelin (0.01 to 10
nmol/L) induced a dose-dependent positive inotropic effect (EC50: 33.1+/-1.5
pmol/L). Moreover, preload-induced increase in dP/dt(max) was significantly
augmented (P<0.05) in the presence of apelin. Inhibition of phospholipase
C (PLC) with U-73122 and suppression of protein kinase C (PKC) with staurosporine
and GF-109203X markedly attenuated the apelin-induced inotropic effect
(P<0.001). In addition, zoniporide, a selective inhibitor of Na+-H+ exchange
(NHE) isoform-1, and KB-R7943, a potent inhibitor of the reverse mode
Na+-Ca2+ exchange (NCX), significantly suppressed the response to apelin
(P<0.001). Perforated patch-clamp recordings showed that apelin did not
modulate L-type Ca2+ current or voltage-activated K+ currents in isolated
adult rat ventricular myocytes. Apelin mRNA was markedly downregulated
in cultured neonatal rat ventricular myocytes subjected to mechanical
stretch and in vivo in two models of chronic ventricular pressure overload.
The present study provides the first evidence for the physiological significance
of apelin in the heart. Our results show that apelin is one of the most
potent endogenous positive inotropic substances yet identified and that
the inotropic response to apelin may involve activation of PLC, PKC, and
sarcolemmal NHE and NCX.
Szokodi I, et al. Circ Res 2002 Sep 6;91(5):434-40
The novel peptide apelin lowers blood pressure via a nitric oxide-dependent
mechanism
Apelin is an endogenous ligand of the human orphan receptor APJ. We detected
apelin-like immunoreactivity in the adipocytes, gastric mucosa, and Kupffer
cells in the liver. We also detected apelin-like immunoreactivity localized
within the endothelia of small arteries in various organs. Further, it
was found that mean arterial pressure after the administration of apelin-12,
apelin-13, and apelin-36 at a dose of 10 nmol/kg in anaesthetized rats
was reduced by 26+/-5, 11+/-4, and 5+/-4 mm Hg, respectively. In the presence
of a nitric oxide (NO) synthase inhibitor, the effect of apelin-12 on
blood pressure was abolished. Furthermore, the administration of apelin-12
(10 nmol/kg) in rats produced a transitory elevation of the plasma nitrite/nitrate
concentration from a basal level of 21.4+/-1.6 to 27.0+/-1.5 microM. Thus,
apelin may lower blood pressure via a nitric oxide-dependent mechanism.
Tatemoto K, et al. Regul Pept 2001 Jun 15;99(2-3):87-92
Apelin-immunoreactivity in the rat hypothalamus and pituitary
With the use of an antiserum against human apelin-36 (Phoenix Pharmaceuticals),
apelin-immunoreactivity (irAP) was detected in neurons and cell processes
of the supraoptic nucleus (SO), paraventricular nucleus (PVH), accessory
neurosecretory nuclei (Acc) and suprachiasmatic nucleus. Strongly labeled
cells/processes were noted in the internal layer of the median eminence,
infundibular stem, anterior and posterior pituitary. Double-labeling the
sections with goat polyclonal neurophysin I-antiserum and rabbit polyclonal
apelin-antiserum revealed a population of magnocellular neurons in the
PVH, SO and Acc expressing both irAP and neurophysin I-immunoreactivity
(irNP), the latter being a marker of oxytocin-containing neurons. By inference,
the AP-positive but irNP-negative magnocellular neurons could be vasopressin-containing.
The presence of irAP in certain hypothalamic nuclei and pituitary suggests
that the peptide may be a signaling molecule released from the hypothalamic-hypophysial
axis.
Brailoiu GC, Dun SL, Yang J, Ohsawa M, Chang JK,
Dun NJ. Neurosci Lett 2002 Jul 26;327(3):193-7
Apelin expression in normal human tissues
Apelin is an endogenous ligand of the human orphan receptor APJ (orphan
G protein-coupled receptor). This peptide is produced through processing
from the C-terminal portion in the pre-proprotein consisting of 77 amino
acid residues and exists in multiple molecular forms. Although the main
physiological functions of apelin have not been clarified yet, it has
been demonstrated that apelin partially suppresses cytokine production
from mouse spleen and, specifically, induces the promotion of extracellular
acidification and inhibition of cAMP production in Chinese hamster ovary
cells. Moreover, it is involved in the regulation of blood pressure and
blood flow. In this study we have analyzed, by immunohistochemistry, apelin
distribution in several human tissues, demonstrating that apelin has a
widespread pattern of expression. These results seem to confirm that apelin
functions widely in various tissues interacting with its specific receptor
APJ.
De Falco M, et al. In Vivo 2002 Sep-Oct;16(5):333-6
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| Matthias J. Kleinz*, Anthony P. Davenport. Regulatory Peptides 118 (2004) 119–125 |
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| Photomicrographs demonstrating
apelin-like immunoreactivity (apelin-LI) in the human heart. Apelin-LI
is expressed in vascular endothelial cells of right atria (a and
b) and left ventricle (c and e), with adjacent sections (d and f)
stained for the endothelial marker von Willebrand factor (vWF).
Apelin-LI was also identified in endocardial endothelial cells lining
the right atrium (g) with an adjacent section stained for vWF (h).
In sections from right atrium (i) no staining was detectable when
the primary antiserum was omitted as negative control (j). M.J. Kleinz, A.P. Davenport / Regulatory Peptides 118 (2004) 119–125 121 |
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Photomicrographs showing apelin-like immunoreactivity
in vascular endothelial cells of blood vessels from kidney (a, b)
and adrenal gland (c) with an adjacent section of adrenal gland
(d), where the primary antiserum was omitted as negative control.
Matthias J. Kleinz*, Anthony P. Davenport. Regulatory Peptides 118 (2004) 119–125 |
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Apelin-like immunoreactivity in vascular endothelial
cells of large conduit vessels. Photomicrographs show staining in
saphenous vein (a) and coronary artery (c) with higher magnification
of the respective vessels in (b) and (d). Matthias J. Kleinz*, Anthony P. Davenport. Regulatory Peptides 118 (2004) 119–125 |
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Specificity of the rabbit-anti-apelin-12
antiserum determined by antiserum dilution ELISA. Microtiter plates
were coated with a fixed amount (1 Ag/ml) of five different peptides,
apelin-36 (o), apelin-13 (.), ghrelin (B), ET-1 (4), angiotensin-II
(5). The antiserum cross-reacted with apelin-36 and apelin-13, but
not with the other peptides. Absorbance (meanFS.E.M.) is plotted
against antiserum dilution as a measure of potency and specificity
of the antibody–antigen interaction. Matthias J. Kleinz*, Anthony P. Davenport. Regulatory Peptides 118 (2004) 119–125 |
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Amino acid sequences of apelin-13 (a) and apelin-36
(b). Dark grey indicates amino acids identical in both peptides.
The N-terminal Pyr1 of (Pyr1) apelin-13 differs from the prepropeptide
sequence as a result of post-translational modification. The antiserum
used for immunocytochemistry was raised against the C-terminal dodecapeptide
common to both peptides, which is indicated in dark grey. Matthias J. Kleinz*, Anthony P. Davenport. Regulatory Peptides 118 (2004) 119–125 |
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| Apelin Receptor APJ Immunohistochemistry |
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Apelin level and distribution
in human left ventricle. A, Left ventricular tissue apelin level
as determined by enzyme immunoassay. The level rose significantly
(p<0.001) after offloading by implantation of a left ventricular
assist device. Units are nanogram per milliliter. B, Immunohistochemical
distribution of apelin. Apelin, labeled reddish-brown, is highly
localized to endothelial and smooth muscle cells in diseased (right)
and normal heart (diseased only shown). Staining of consecutive
sections with platelet-endothelial cell adhesion molecule (CD31,
middle) confirms the specificity of this localization. Control
panels (left) represent sections where incubation in primary antibody
was omitted. Chen MM, et al. Circulation. 2003 Sep 23;108(12):1432-9.
Epub 2003 Sep 08 |
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Plasma apelin levels
in heart failure. A. There were significant increases in the plasma
level of apelin as determined by enzyme immunoassay in early heart
failure through NYHA class 2 (p<0.02). In later stage diseases,
the mean level id lower, although this change is not significant.
Class 4 patients (n=7) are combined with class 3 (from left to
right, n=34, 24, 12, and 38). B, Apelin rises in mild-to-moderate
left ventricular dysfunction but falls in severe disease (p<0.02
for both). Normal is defined as a left ventricular ejection fraction
greater than 45%, mild to moderate is 25% to 45% and severe is
less than 25% (from left to right, n=42, 28, 40). Chen MM, et
al. Circulation. 2003 Sep 23;108(12):1432-9. Epub 2003 Sep 08 |
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| Foldes G, et al. Biochem Biophys Res Commun. 2003 Aug 29;308(3):480-5 | |||||||||||||||||||||||
| Tissue and blood sampling.
After removal, cardiac tissue samples were blotted dry, immersed
in liquid nitrogen, and stored at -80 °C until assayed. For
plasma sampling, blood was taken before surgery after 30 min
bed rest and collected into chilled tubes containing EDTA. The plasma
was separated by centrifugation at +4 °C and kept at -80 °C
until assayed.
Radioimmunoassay for apelin. Immunoreactive apelin (ir-apelin) was determined from extracted plasma and right atrial and left ventricular samples using an apelin-36 radioimmunoassay kit (Phoenix, Cat-No. RK-057-15). Apelin assay was performed according to the manufacturer's instructions. The sensitivity of assay was 1 fmol/tube. Tissue peptide levels are expressed as a concentration per mg wet weight. HPLC analysis. Gel filtration high
performance liquid chromatography (GF-HPLC) and apelin radioimmunoassay
were used in order to characterize the molecular form of immunoreactive
apelin in plasma and tissue extracts. Aliquots of the atrial tissue
homogenates, used for RNA extraction, from healthy subjects and
patients with heart failure were diluted to 400 |
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Atrial and ventricular immunoreactive apelin levels Apelin-like immunoreactivity was detected in the heart of organ donors, being over 200-fold higher in the right atria than in the left ventricles (650 ?nbsp;145 pg/mg, n=5 and 2.8 ?nbsp;0.6 pg/mg, n=10, respectively). There was a tendency for left ventricular ir-apelin levels to be higher in patients with heart failure due to coronary heart disease (4.4 ?nbsp;0.5 pg/mg, p=0.07) and idiopathic dilated cardiomyopathy (3.8 ?nbsp;0.9 pg/mg, p=0.4) than those in controls, but these changes were not statistically significant (Fig. 1B). Interestingly, atrial ir-apelin levels were significantly decreased in patients with heart failure (Fig. 2B). |
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Plasma apelin levels in normal subjects and in patients with heart failure Immunoreactive apelin was found to be present in normal human plasma (mean, 89.8 ?nbsp;5.3 pg/ml, n=6). Plasma levels of ir-apelin were significantly decreased in patients with heart failure due to coronary heart disease compared to normal subjects (in NYHA III: 71 ?nbsp;6 pg/ml, p<0.05). Plasma ir-apelin levels showed significant correlation to atrial ir-apelin levels (R=0.4, n=38, p<0.05). |
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| Fig. 01 Left ventricular apelin mRNA (A), immunoreactive
apelin-36 (B), and APJ receptor mRNA (C) levels in control subjects
(n=9) and patients with end-stage heart failure due to coronary
heart disease (CHD, n=7) and idiopathic dilated cardiomyopathy
(IDC, n=6). The mRNA results are expressed as ratios to 18S
RNA determined by TaqMan real-time quantitative RT-PCR analysis. Bars
indicate means ?nbsp;SEM. *p<0.05 and **p<0.01
vs. control subjects. Foldes G, et al. Biochem Biophys Res Commun. 2003 Aug 29;308(3):480-5 |
Fig.02 Right atrial apelin
mRNA (A), immunoreactive apelin-36 (B), and APJ receptor mRNA (C)
levels in control subjects (n=6) and patients with heart failure
(NYHA functional class II or III) due to coronary heart disease (CHD,
n=38). Bars indicate means ?nbsp;SEM. *p<0.05
and **p<0.01 vs. control subjects. Foldes G, et al. Biochem Biophys Res Commun. 2003 Aug 29;308(3):480-5 |
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| Fig. 3. Gel filtration HPLC analysis
of immunoreactive apelin in plasma (A,B) and atrial extracts (C,D)
of a healthy control (A,C) and a patient with heart failure (B,D).
The arrows denote elution positions of bovine serum albumin (V0),
apelin-36, and 125I-, used for the calibration
of the column. Foldes G, et al. Biochem Biophys Res Commun. 2003 Aug 29;308(3):480-5 |
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| IDC, idiopathic dilated cardiomyopathy; CCHD, coronary
heart disease. Foldes G, et al. Biochem Biophys Res Commun. 2003 Aug 29;308(3):480-5 |
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An
alignment of amino acid sequences of rat preproapelin with human
and bovine preproapelin. Conserved amino acids are shown boxed.
The mature apelin peptide is shaded. Numeric amino acid positions
are indicated on the right. The GenBank accession numbers for rat
and human preproapelin are AF179679 and AF179680, respectively.
B: An alignment of amino acid sequences of human apelin and
angiotensin II. Conserved amino acids are shown boxed. C:
The genomic structure of the human preproapelin gene as found in
the human PAC 454M7 clone (GenBank accession no. AL022162). Nucleotide
positions of PAC 454M7 defining preproapelin gene exons (boxes)
are shown at the top. The ORF is shown in black, with the nucleotide
positions of the start and stop codons shown at bottom. Lee, Dennis K., et al. Characterization of Apelin, the Ligand for the APJ Receptor. Journal of Neurochemistry 74 (1), 34-41. |
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| Northern
blot analysis of the distribution of preproapelin mRNA in human
(A) and rat (B and C) tissues. Each lane contained
10  g
of poly(A)+ RNA isolated from various tissues, with the
exception of rat pituitary (7.5 g),
olfactory tubercle (7.8 g),
septum (5 g),
and liver (7 g).
Lee, Dennis K., et al. Characterization of Apelin, the Ligand for the APJ Receptor. Journal of Neurochemistry 74 (1), 34-41. |
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| Darkfield autoradiograms of coronal sections of rat brain showing the localization of preproapelin mRNA, at various distances from bregma according to the stereotactic coordinates of Paxinos and Watson (1982). Shown are representative sections at levels relative to the bregma at -0.3 mm (A), -0.5 mm (B), -1.8 mm (C), -2.8 mm (D), -3.9 to -4.2 mm (E), and -5.8 mm (F). 3v, third ventricle; 4v, fourth ventricle; 7, facial nucleus; AC, anterior cingulate cortex; AD, anterodorsal thalamic nucleus; AM, anteromedial thalamic nucleus; APT, anterior pretectal area; AUD, auditory area; CA, field of Ammon's horn; Ch, choroid plexus; CL, centrolateral thalamic nucleus; CP, caudate putamen; DG, dentate gyrus; DK, nucleus of Darkschewitsch; DM, dorsomedial hypothalamic nucleus; FP, frontoparietal cortex; IC, inferior colliculus; IPN, interpeduncular nucleus; LG, lateral geniculate complex; LS, lateral septal nucleus; MA, magnocellular preoptic nucleus; MD, mediodorsal thalamic nucleus; MEA, medial amygdaloid nucleus; MEPO, median preoptic nucleus; MG, medial geniculate nucleus; MH, medial habenular nucleus; MPO, medial preoptic area; OB, olfactory bulb; OT, olfactory tubercle; PAG, periaqueductal gray; PB, parabrachial nucleus; PE, periventricular hypothalamic nucleus; Pi, pineal gland; PO, primary olfactory cortex; PT, parietal region; PVN, paraventricular hypothalamic nucleus; RS, retrosplenial area; S5, sensory root of the trigeminal nerve; SC, superior colliculus; SF, septofimbrial nucleus; SH, septohypothalamic nucleus; SO, supraoptic hypothalamic nucleus; SS, primary somatosensory area; ST/STH, subthalamic nucleus; SUB, dorsal subiculum; TS, triangular septal nucleus; V, vestibular nucleus; VAL, ventral anterior-lateral complex thalamus; VIS, primary visual area; VM, ventromedial thalamic nucleus; VP, ventroposterior thalamic nucleus; ZI, zona incerta. Lee, Dennis K., et al. Characterization of Apelin, the Ligand for the APJ Receptor. Journal of Neurochemistry 74 (1), 34-41. |
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| Darkfield
autoradiograms of sagittal and coronal sections of rat brain showing
the localization of preproapelin mRNA (A) and APJ receptor
mRNA (B-E). A and B show lateral representative sections
at 1.77 and 0.4 mm, respectively. Also shown are representative
sections at levels relative to the bregma at 1.2 mm (C), -1.8 mm
(D), and -4.8 mm (E). See Fig.
3 for abbreviation definitions. Lee, Dennis K., et al. Characterization of Apelin, the Ligand for the APJ Receptor. Journal of Neurochemistry 74 (1), 34-41. |
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Blood
pressure and heart rate changes after 1 and 2 g/300
g B.W. intravenous apelin injection into rats (n = 5). Values are
shown as means ?SEM. Lee, Dennis K., et al. Characterization of Apelin, the Ligand for the APJ Receptor. Journal of Neurochemistry 74 (1), 34-41. |
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Water consumption after intraperitoneal injection of 100 g
of apelin into rats (n = 18), recorded at 30-min intervals. An asterisk
indicates a significant difference in water consumption between
vehicle- and apelin-injected rats. Values are shown as means ?SEM.
Lee, Dennis K., et al. Characterization of Apelin, the Ligand for the APJ Receptor. Journal of Neurochemistry 74 (1), 34-41. |
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Dr. Nae J. Dun, East Tennessee State University |
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Rat hypothalamus was stained by Anti-Apelin-36 (Human) Serum (H-057-15) |
Reference: Neurosci Lett 2002 Jul 26;327(3):193-7 | ||||||||||||||||||||||
l
of 40% acetonitrile in aqueous 0.1% TFA. Plasma samples (1 ml)
were extracted with SepPak C18 cartridges, dried, and reconstituted
in 400 
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The effects of centrally administered apelin-13 on food intake, water
intake and pituitary hormone release in rats
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.
Taheri S, et al. Biochem Biophys Res Commun
2002 Mar 15;291(5):1208-12
Prepro-Apelin (Human) Sequence
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An Enteric Peptide |
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Apelin's Cardiovascular and Obesity-related Functions |
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Apelin & HIV Entry |
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Apelin Receptor APJ Antibody |
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Apelin-related Products |