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Cocaine and Amphetamine Related Transcript (CART) related products |
Cocaine and Amphetamine Regulated Transcript (CART), brilliantly
identified by Douglass and co-workers is an anorectic peptide regulated
by leptin. Fasting animals
show a pronounced decrease in CART mRNA expression in the arcuate nucleus,
an area of the brain known to be associated with feeding behavior.
In animal models with disrupted leptin signalling, CART mRNA is
almost absent in the arcuate nucleus.
ICV administration of CART inhibits both normal and starvation-induced
feeding and completely blocks the feeding response induced by NPY.
Antisera directed against CART increases feeding in normal rats.
Indications are that CART may be an endogenous inhibitor of food
intake (Kristensen et al, 1998).
Central administration of cocaine- and amphetamine-regulated transcript
inhibits food intake in chicks
The present study was done to clarify whether intracerebroventricular
(ICV) injection of cocaine- and amphetamine-regulated transcript (CART)
affects feeding in chicks. ICV injection of CART significantly inhibited
fasting-induced feeding of broiler chicks. In layer chicks, on the other
hand, CART inhibited food intake in birds with ad libitum access to feed
but only weakly affected intake of fasted birds. In addition, the ICV
injection of CART attenuated neuropeptide Y (NPY)-induced feeding in both
broiler and layer chicks. These results indicate that CART is one of the
important regulators of feeding in chicks, but the suppressive effect
on feeding is somewhat different between strains. Furthermore, the present
study also demonstrates that CART interacts with NPY in the central nervous
system to regulate feeding in chicks.
Tachibana T et al. Neurosci Lett, February 13, 2003;
337 (3): 131-4
Cocaine- and amphetamine-regulated transcript peptide produces anxiety-like
behavior in rodents
Cocaine- and amphetamine-regulated transcript (CART) peptide (CART-(55-102))
is involved in the suppression of food intake. We now report that CART-(55-102)
is involved in anxiety in rodents. Intracerebroventricularly administered
CART-(55-102) as well as intraperitoneal administration of N-methyl-beta-carboline-3-carboxamide
(FG-7142), a selective GABA(A)/benzodiazepine receptor inverse agonist,
reduced time spent in the open arms in the elevated plus-maze task in
mice. CART-(55-102)-induced anxiogenic-like behavior in this task was
attenuated by widely prescribed anxiolytics such as diazepam and buspirone.
Likewise, CART-(55-102) and FG-7142 significantly reduced social interaction
in mice. Both diazepam and buspirone significantly reversed CART-(55-102)-induced
anxiogenic-like behavior in social interaction tests. By contrast, another
biologically active CART peptide, CART-(62-102), was without effect in
the elevated plus-maze task in mice. Moreover, intracerebroventricular
administration of CART-(55-102) markedly increased the firing rate of
locus coeruleus neurons in single unit recording in anesthetized rats.
As CART-(55-102) produced anxiety-like effects in rodents, this peptide
may possibly be involved in anxiety and stress-related behavior.
Chaki S et al. Eur J Pharmacol, March 7, 2003; 464(1):
49-54
Chronic central infusion of cocaine- and amphetamine-regulated transcript (CART 55-102): effects on body weight homeostasis in lean and high-fat-fed obese rats
BACKGROUND
Cocaine- and amphetamine-regulated transcript (CART) is expressed within
hypothalamic nuclei implicated in the regulation of feeding behaviour.
It is up-regulated by leptin, and CART-derived peptides acutely inhibit
food intake.
OBJECTIVE
The present study was designed to assess the long-term effects of central
CART administration on food intake, body weight, plasma levels of glucose,
insulin, leptin, free fatty acids and triglycerides, and on fuel utilisation
in normal and high-fat-fed obese rats.
DESIGN
Normal and high-fat-fed obese rats were cannulated intracerebroventricularly
(i.c.v.) and infused for 6 days with CART (55-102) or its vehicle. At
day 4, animals were placed in an indirect calorimeter for a 24 h period
during which the respiratory quotient and the energy expenditure were
determined hourly.
RESULTS
In both normal and obese animals, the chronic i.c.v. infusion of CART
(55-102) had marked, sustained inhibitory effects on food intake and body
weight gain that were accompanied by decreases in plasma insulin and leptin
levels. Using indirect calorimetry, it was observed that CART infusion
promoted an increase in lipid oxidation in normal and in obese animals,
although this increase reached statistical significance only in the obese
group. The hypothalamic CART mRNA expression was found to be higher in
obese rats (displaying hyperleptinaemia) than in normal animals. CONCLUSION:
The data together show that chronic i.c.v. CART infusion is effective
in inhibiting food intake, favouring lipid oxidation and limiting fat
storage, both in normal and high-fat-diet-induced obese rats. The CART
pathway thus seems to be an important determinant of body weight homeostasis
in normal animals as well as in a model of nutritionally induced obesity.
Rohner-Jeanrenaud et al. Int J Obes Relat Metab
Disord 2002 Feb;26(2):143-9
Hypothalamic CART and serum leptin levels are reduced in the anorectic (anx/anx) mouse
Cocaine- and amphetamine-regulated transcript (CART) is expressed in
the hypothalamus, and putative peptides encoded by CART potently inhibit
feeding when administered centrally. CART is strongly down-regulated in
the lateral hypothalamic area and the arcuate nucleus in animal models
of obesity with disrupted leptin signaling. Here we have used in situ
hybridization and immunohistochemistry to study CART expression in mice
homozygous for the anorexia (anx) mutation which are characterized by
a much reduced food intake and premature death. anx/anx mice had significantly
decreased levels of CART mRNA label and peptide-immunoreactive cell bodies
and fibers in the arcuate nucleus and a lower number of detectable CART-expressing
cells in the dorsomedial hypothalamic nucleus/lateral hypothalamic area.
Moreover, serum leptin levels were significantly lower in anx/anx mice
compared to normal littermates, most likely due to the prominent depletion
of body fat in these animals. The decrease in the anorexigenic agents
leptin and CART, may reflect a compensatory down-regulation in response
to the energy-deprived state of anx/anx mice. Alternatively, the reduced
arcuate CART expression may be a consequence of a molecular defect in
the arcuate nucleus of these animals.
Johansen JE, Broberger C, Lavebratt C, Johansson
C, Kuhar MJ, Hokfelt T, Schalling M. Hypothalamic CART and serum leptin
levels are reduced in the anorectic (anx/anx) mouse. Brain Res Mol Brain
Res 2000 Dec 8;84(1-2):97-105
Hypothalamic CART is a new anorectic peptide regulated by leptin
The mammalian hypothalamus strongly influences ingestive behaviour through
several different signalling molecules and receptor systems. Here we show
that CART (cocaine- and amphetamine-regulated transcript), a brain-located
peptide, is a satiety factor and is closely associated with the actions
of two important regulators of food intake, leptin and neuropeptide Y.
Food-deprived animals show a pronounced decrease in expression of CART
messenger RNA in the arcuate nucleus. In animal models of obesity with
disrupted leptin signalling, CART mRNA is almost absent from the arcuate
nucleus. Peripheral administration of leptin to obese mice stimulates
CART mRNA expression. When injected intracerebroventricularly into rats,
recombinant CART peptide inhibits both normal and starvation-induced feeding,
and completely blocks the feeding response induced by neuropeptide Y.
An antiserum against CART increases feeding in normal rats, indicating
that CART may be an endogenous inhibitor of food intake in normal animals.
Kristensen P, Judge ME, Thim L, Ribel U, Christjansen
KN, Wulff BS, Clausen JT, Jensen PB, Madsen OD, Vrang N, Larsen PJ, Hastrup
S.
Nature 1998 May 7;393(6680):72-6
Additional CART References:
- Dun SL, Ng YK, Brailoiu GC, Ling EA, Dun NJ. Cocaine- and amphetamine-regulated transcript peptide-immunoreactivity in adrenergic C1 neurons projecting to the intermediolateral cell column of the rat. J Chem Neuroanat. 2002 Feb;23(2):123-32.
- Dun SL, Castellino SJ, Yang J, Chang JK, Dun NJ. Cocaine- and amphetamine-regulated transcript peptide-immunoreactivity in dorsal motor nucleus of the vagus neurons of immature rats. Brain Res Dev Brain Res. 2001 Nov 26;131(1-2):93-102.
- Dun SL, Chianca DA Jr, Dun NJ, Yang J, Chang JK. Differential expression of cocaine- and amphetamine-regulated transcript-immunoreactivity in the rat spinal preganglionic nuclei. Neurosci Lett. 2000 Nov 24;294(3):143-6.
- Dun NJ, Dun SL, Wong PY, Yang J, Chang J. Cocaine- and amphetamine-regulated transcript peptide in the rat epididymis: an immunohistochemical and electrophysiological study. Biol Reprod. 2000 Nov;63(5):1518-24.
- Ohsawa M, Dun SL, Tseng LF, Chang J, Dun NJ. Decrease of hindpaw withdrawal latency by cocaine- and amphetamine-regulated transcript peptide to the mouse spinal cord. Eur J Pharmacol. 2000 Jul 7;399(2-3):165-9.
- Dun NJ, Dun SL, Kwok EH, Yang J, Chang J. Cocaine- and amphetamine-regulated transcript-immunoreactivity in the rat sympatho-adrenal axis. Neurosci Lett. 2000 Apr 7;283(2):97-100.
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Cocaine and Amphetamine Related Transcript (CART) related products |
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Cocaine- and Amphetamine-Regulated Transcript Peptide in the Rat Epididymis: An Immunohistochemical and Electrophysiological Study a
Department of Pharmacology, James H. Quillen College of Medicine,
East Tennessee State University, Johnson City, Tennessee 37614 Biology of Reproduction 63, 1518-1524 (2000) |
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| Photomicrographs of sections through the vas deferens, cauda, corpus, and caput of epididymis labeled with CART antisera using the fluorescent method. A and B) Low- and higher-magnification views of a longitudinal section of vas deferens in which CART-LI is seen in numerous varicose fibers surrounding the lumen. C and D) Low- and higher-magnification views of a section of cauda where varicose CART-LI fibers are distributed between the tubules and underneath the epithelium. E) Few CART-LI fibers are seen in this corpus section. F) CART-LI is virtually absent in this caput section. Bar = 100 µm (A, C, and F) and 50 µm (B, D, and E) |
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| Photomicrographs of sections through rat major pelvic ganglia labeled with CART antisera or CART antisera preabsorbed with the CART peptide 55–102 using the immunoperoxidase method. A) Low-magnification view showing that numerous ganglion cells are strongly labeled. B) Higher-magnification view of an area outlined in A in which CART-LI was detected in some of the smaller-diameter ganglion cells. Some of the larger-diameter ganglion cells, which are not labeled, are invested with varicose CART-LI endings (arrows). C) A section of major pelvic ganglion showing clusters of intensely labeled, small-diameter, CART-positive cells, which are boxed in. D) A section of major pelvic ganglion processed with CART antisera preabsorbed with the peptide (10 µg/ml). Immunoreactivity is not detectable in this section. Bar = 100 µm (A and D), and 25 µm (B), and 50 µm (C) |
| Immunohistochemistry Rats were anesthetized with urethane (1.2 g/kg i.p.) and intracardially perfused with 0.1 M PBS, followed by freshly prepared, 4% paraformaldehyde in PBS. The epididymis, vas deferens and major pelvic ganglia were removed, postfixed for 2 h, and immersed in 30% sucrose/PBS overnight. Tissues were sectioned to 40 µm with a Vibratome (Technical Products International, Inc., St. Louis, MO) and processed for CART-LI by the avidin-biotin complex (ABC) or fluorescent techniques. In addition, some sections were set aside for double-labeling experiments, in which only the fluorescent method was used. In the ABC method, tissues were first treated with 3% H2O2 to quench endogenous peroxidase, washed several times in Tris-buffered saline, and blocked with 10% normal goat sera (Vector Laboratories, Burlingame, CA). Tissues were incubated in the primary antibody to CART peptide fragment 55–102 (1:10 000 dilution with 0.4% Triton X-100 and 1% BSA in PBS) for 48 h at 4°C with gentle agitation. The CART antiserum, a rabbit polyclonal from Phoenix Pharmaceuticals, Inc. (Mountain View, CA), exhibits 100% cross-reactivity with the rat CART peptide 55–102 (Phoenix Pharmaceuticals). After thorough rinsing, sections were incubated with biotinylated antirabbit immunoglobulin (Ig) G (1:150 dilution; Vector Laboratories) for 2 h. Sections were rinsed with PBS and incubated in ABC solution for 1 h (1:100 dilution; Vector Laboratories). After several rinses in Tris-buffered saline, sections were developed in diaminobenzidine-H2O2 solution and washed for at least 2 h with Tris-buffered saline. Sections were mounted on slides with 0.25% gel alcohol, air-dried, dehydrated with absolute alcohol followed by xylene, and coverslipped with Permount (Fisher Scientific, Pittsburgh, PA). For the fluorescent method, tissues were first blocked with 10% normal goat sera and then incubated with CART antisera (1:2 000 dilution with 0.4% Triton X-100 and 1% BSA in PBS) for 48 h in a cold room with gentle agitation. After several washes with PBS, sections were incubated with biotinylated antirabbit IgG (1:50 dilution; Vector Laboratories) for 2 h. After several washes in PBS, tissues were incubated with Fluorescein Avidin D (1:50 dilution; Vector Laboratories). Lastly, tissues were washed for 30 min with PBS, mounted in Citifluor (Ted Pella, Redding, CA), and coverslipped. In the case of double-labeling studies, the technique of sequential
labeling with primary antisera from two different hosts was
used. Tissues were first processed for fluorescent CART-LI
as described earlier. Thereafter, tissues were washed with
PBS for at least 2 h, blocked with normal horse sera, and then
incubated with tyrosine hydroxylase (TH) antisera (1:500 dilution
with 0.4% Triton X-100 and 1% BSA in PBS) for 48 h in
a cold room with gentle agitation. The TH antiserum was a mouse
monoclonal from Chemicon International, Inc. (Temecula, CA),
and the specificity of the antibody has been extensively evaluated.
After washing with PBS for 30 min, tissues were incubated
with Avidin Texas Red (Vector Laboratories) for 4 h,
washed for 30 min with PBS, mounted in Citifluor, and coverslipped.
Sections were examined with a Nikon EC600 fluorescent microscope
and photographed. |
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Cocaine and Amphetamine Related Transcript (CART) related products |
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