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Nae J. Dun - One of the best experts on this subject based on the ideXlab platform.
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Expression and activity of cocaine- and Amphetamine-Regulated Transcript peptide1–39 in the rat
Regulatory Peptides, 2006Co-Authors: Siok L. Dun, Jun Yang, Jaw Kang Chang, Eugen Brailoiu, Wei-kung Hsieh, Chih-chia Lai, Nae J. DunAbstract:Abstract Cocaine- and Amphetamine-Regulated Transcript (CART) peptide consists of a family of peptides. Expression of the peptide fragment CART1–39 was explored in the rat using an antiserum directed against CART1–39 of the short form of the human CART prohormone. CART1–39-immunoreactivity, herein referred to as irCART, was detected in the rat central and peripheral nervous tissues with a pattern similar to that labeled with the antiserum CART55–102 or CART79–102. For example, irCART cells were detected in the hypothalamus, pons, medulla oblongata, spinal cord, and adrenal medulla. In urethane-anesthetized rats, CART1–39 (0.05 to 2 nmol) by intrathecal injection did not cause a significant change of blood pressure or heart rate, but potentiated the pressor effects of glutamate injected intrathecally. Lastly, the effect of CART1–39 on intracellular calcium concentrations [Ca2+]i was assessed and compared to that caused by CART55–102 in cultured rat cortical neurons using the microfluorimetric method. CART1–39 (100 nM) induced two types of responses in a population of cortical neurons: 1) a slowly rising increase in [Ca2+]i superimposed with oscillations, and 2) a fast increase followed by a sustained increase of [Ca2+]i. CART55–102 caused only a slowly rising increase in [Ca2+]i in cortical neurons. Our result shows that the expression pattern of irCART in the rat nervous system and the potentiating action of CART1–39 on glutamate-induced pressor response is similar to that reported for CART55–102; but the calcium mobilizing action of CART1–39 differs from that of CART55–102, suggesting the possible existence of multiple CART receptors coupled to different calcium signaling pathways.
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Cocaine- and Amphetamine-Regulated Transcript peptide and sympatho-adrenal axis.
Peptides, 2006Co-Authors: Siok L. Dun, G. Cristina Brailoiu, Jun Yang, Jaw Kang Chang, Nae J. DunAbstract:Cocaine- and Amphetamine-Regulated Transcript peptide (CART) is constitutively expressed in discrete regions of the mammalian central and peripheral nervous system. Immunohistochemical studies reveal a well-defined network of CART-immunoreactive (irCART) neurons organized along the sympatho-adrenal axis. Sympathetic preganglionic neurons, but not parasympathetic preganglionic neurons, in the lateral horn area are CART-positive; which in turn innervate postganglionic neurons in the paravertebral and prevertebral sympathetic ganglia as well as the adrenal medulla. A population of chromaffin cells in the adrenal medulla is CART-positive; whereas, postganglionic neurons are not. Sympathetic preganglionic neurons themselves are contacted by irCART cell processes arising from neurons in the arcuate nucleus, the retrochiasmatic nucleus and the rostral ventrolateral medulla. Results from several recent studies suggest CART directly excites neurons along the sympathetic neural axis or indirectly by potentiating the action of glutamate on NMDA receptors, as evidenced by an elevation of blood pressure and heart rate following intracerebroventricular, intracisternal or intrathecal administration of the peptide to anesthetized rats or conscious rabbits.
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Cocaine- and Amphetamine-Regulated Transcript peptide attenuates phenylephrine-induced bradycardia in anesthetized rats.
American journal of physiology. Regulatory integrative and comparative physiology, 2003Co-Authors: Phouangmala Scruggs, Siok L. Dun, Nae J. DunAbstract:The present study was undertaken to investigate the origin of cocaine- and Amphetamine-Regulated Transcript (CART) peptide immunoreactive (irCART) fibers observed in the nucleus of the solitary tract (NTS) and assess the role of CART peptide on phenylephrine (PE)-induced baroreflex. Immunohistochemical and retrograde tract-tracing studies showed that some of the irCART fibers observed in the NTS may have their cell bodies in the nodose ganglia. In urethane-anesthetized rats, intracisternal or bilateral intra-NTS microinjection of the CART peptide fragment 55-102 (0.1-3 nmol), referred to herein as CARTp, consistently and dose dependently attenuated PE-induced bradycardia. CARTp, in the doses used here, caused no significant changes of resting blood pressure or heart rate. Bilateral intra-NTS injections of CART antibody (1:500) potentiated PE-induced bradycardia. Injections of saline, normal rabbit serum, or concomitant injection of CARTp and CART antiserum into the NTS caused no significant changes of PE-induced baroreflex. The result suggests that endogenously released CARTp from primary afferents or exogenously administered CARTp modulates PE-induced baroreflex.
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Differential expression of cocaine- and Amphetamine-Regulated Transcript-immunoreactivity in the rat spinal preganglionic nuclei
Neuroscience letters, 2000Co-Authors: Siok L. Dun, Jun Yang, Nae J. Dun, Deoclécio A. Chianca, Jaw Kang ChangAbstract:The distribution of cocaine- and Amphetamine-Regulated Transcript-like immunoreactivity (CART-LI) was investigated in the rat spinal cords with the use of an antiserum against the CART peptide fragment 55-102. CART-LI fibers were concentrated in the superficial layers of the dorsal horn of all segments. In addition to CART-LI fibers, intensely labeled somata were detected in the intermediolateral cell column (IML) and other sympathetic preganglionic nuclei of the thoracolumbar segments. In the lumbosacral segments, CART-LI fibers but not somata were seen in the sacral parasympathetic nucleus. Double-labeling the spinal sections with choline acetyltransferase (ChAT)-antisera and CART-antisera revealed that the large majority of ChAT-positive somata in the sympathetic preganglionic nuclei were CART-positive, whereas ChAT-positive somata in the parasympathetic preganglionic nuclei were CART-negative. Our results show that CART-LI is selectively expressed in a population of sympathetic preganglionic neurons (SPNs), but not in parasympathetic preganglionic neurons (PPNs) of the rat.
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Cocaine- and Amphetamine-Regulated Transcript-immunoreactivity in the rat sympatho-adrenal axis.
Neuroscience letters, 2000Co-Authors: Nae J. Dun, Siok L. Dun, Jun Yang, Ernest H. Kwok, Jaw Kang ChangAbstract:Distribution of cocaine- and Amphetamine-Regulated Transcript-like immunoreactivity (CART-LI) was studied in the rat spinal cord, sympathetic ganglia and adrenal glands by immunohistochemical methods, utilizing a polyclonal antiserum raised against the CART peptide fragment 55-102. CART-LI was detected in nerve fibers and in basket-like terminals surrounding many postganglionic neurons of the superior cervical ganglion (SCG), stellate, paravertebral and prevertebral ganglia. Postganglionic neurons exhibited low or non-detectable levels of CART-LI. Surgical sectioning of the cervical sympathetic trunk for 6-7 days resulted in a nearly complete loss of CART-LI fibers and terminals in the SCG. In the adrenal gland, CART-LI nerve fibers formed a plexus underneath the capsule, some of which bifurcated and made a sharp turn toward the adrenal medulla, where clusters of chromaffin cells were intensely labeled. The detection of CART-LI in sympathetic ganglia and adrenal glands extends the previous observation of the presence of CART-LI in sympathetic preganglionic neurons and further supports the notion that CART peptide(s) may function as a signaling molecule in the sympatho-adrenal axis.
Michael J Kuhar - One of the best experts on this subject based on the ideXlab platform.
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Wake promoting effects of cocaine and Amphetamine-Regulated Transcript (CART).
Neuropeptides, 2010Co-Authors: Glenda L. Keating, Michael J Kuhar, Donald L. Bliwise, David B. RyeAbstract:Abstract Cocaine- and Amphetamine-Regulated Transcript (CART) peptides modulate anxiety, food intake, endocrine function, and mesolimbic dopamine related reward and reinforcement. Each of these disparate behaviors takes place during the state of wakefulness. Here, we identify a potential wake promoting role of CART by characterizing its effects upon sleep/wake architecture in rats. Dose-dependent increases in wake were documented following intracerebroventricular CART 55–102 administered at the beginning of the rat’s major sleep period. Sustained wake was observed for up to 4 h following delivery of 2.0 μg of CART peptide. The wake promoting effect was specific to active CART 55–102 because no effect on sleep/wake was observed with the inactive form of the peptide. Increased wake was followed by robust rebound in NREM and REM sleep that extended well into the subsequent lights-off, or typical wake period, of the rat. These findings point to a potential novel role for CART in regulating wakefulness.
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Studies of cocaine- and Amphetamine-Regulated Transcript (CART) knockout mice.
Peptides, 2006Co-Authors: Mark C Moffett, Lisa M. Stanek, Jill Harley, George A. Rogge, Mark A. Asnicar, Hansen Hsiung, Michael J KuharAbstract:CART (cocaine- and Amphetamine-Regulated Transcript) peptides are neuropeptides expressed throughout the central nervous system and have been implicated in a variety of physiological processes. Research on the many physiological processes involving CART peptide have been somewhat limited by the lack of an identified CART antagonist. Development of CART peptide deficient mice has allowed scientists to further explore the many functions of CART peptide. This review briefly summarizes recent findings in the literature characterizing CART peptide deficient mice.
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CART (cocaine- and Amphetamine-Regulated Transcript) peptide receptors: specific binding in AtT20 cells.
European journal of pharmacology, 2005Co-Authors: Aleksandra Vicentic, Anita Lakatos, Michael J KuharAbstract:Given previous evidence for CART (cocaine- and Amphetamine-Regulated Transcript) signaling in AtT20 cells, the binding of [125I]-CART61-102 was characterized in these cells. The binding was specific, saturable, dependent on time, pH, temperature and protein concentration, with a Bmax of 101.4+/-8.8 fmol/mg protein and a Kd of 21.9+/-8.0 pM. Only active CART55-102, but not other peptides or drugs, inhibited the [125I]-CART61-102 binding. These data are the first demonstration of specific receptor binding for CART peptides.
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The Leu34Phe ProCART Mutation Leads to Cocaine- and Amphetamine-Regulated Transcript (CART) Deficiency: A Possible Cause for Obesity in Humans
Endocrinology, 2005Co-Authors: Tulin Yanik, Michael J Kuhar, Geraldina Dominguez, Emanuele Miraglia Del Giudice, Y. Peng LohAbstract:Cocaine- and Amphetamine-Regulated Transcript (CART) is an anorexigenic neuropeptide synthesized in the hypothalamus. A Leu34Phe missense mutation in proCART has been found in an obese family in humans. Here we show that humans bearing the Leu34Phe mutation in proCART have severely diminished levels of bioactive CART, but elevated amounts of partially processed proCART in their serum. Expression of wild-type proCART in AtT-20 cells showed that it was sorted to the regulated secretory pathway, a necessity for proper processing to bioactive CART. However, expressed Leu34Phe proCART was missorted, poorly processed, and secreted constitutively. The defective intracellular sorting of Leu34Phe proCART would account for the reduced levels of bioactive CART in affected humans. These results suggest that the obesity observed in humans bearing the Leu34Phe mutation could be due to a putative deficiency in hypothalamic bioactive CART.
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A cocaine-and-Amphetamine-Regulated-Transcript peptide projection from the lateral hypothalamus to the ventral tegmental area.
Neuroscience, 2005Co-Authors: Kelly B. Philpot, Stephanie Dallvechia-adams, Yoland Smith, Michael J KuharAbstract:Abstract Cocaine-and-Amphetamine-Regulated-Transcript peptides play a role in the modulation of feeding and psychomotor stimulant-like behaviors. The ventral tegmental area and the lateral hypothalamus are likely structures where cocaine-and-Amphetamine-Regulated-Transcript peptides mediate both of these functions. Although lateral hypothalamus inputs to the ventral tegmental area have long been known, the chemical nature of this pathway remains poorly understood. To address this issue, we tested the possibility that cocaine-and-Amphetamine-Regulated-Transcript peptide-containing neurons in the lateral hypothalamus project to the ventral tegmental area using the retrograde transport of cholera toxin subunit B combined with cocaine-and-Amphetamine-Regulated-Transcript peptide immunostaining. The largest density of retrogradely-labeled neurons in the hypothalamus after cholera toxin subunit B injection in the ventral tegmental area was found, ipsi- and contralaterally, in the lateral hypothalamus/perifornical area, although substantial numbers of retrogradely-labeled cells were also found in the medial preoptic area, lateral preoptic area, paraventricular nucleus, dorsomedial hypothalamus and ventromedial hypothalamus. More than 80% of the retrogradely-labeled cocaine-and-Amphetamine-Regulated-Transcript peptide-immunoreactive neurons in the hypothalamus were found in the lateral hypothalamus/perifornical area both ipsilateral and contralateral to the injection sites. Although retrogradely-labeled neurons were seen in the amygdala, locus coeruleus, and raphe nucleus, none of them displayed cocaine-and-Amphetamine-Regulated-Transcript peptide immunoreactivity. Therefore, the hypothalamic projection to the ventral tegmental area provides a substrate whereby cocaine-and-Amphetamine-Regulated-Transcript peptides could mediate the rewarding aspects of feeding and psychomotor stimulant-like behaviors. These findings, combined with the fact that the lateral hypothalamus receives strong inputs from the shell of the nucleus accumbens and ventral pallidum, suggest that these structures are part of integrative functional loops that control reward and appetitive behaviors.
Jaw Kang Chang - One of the best experts on this subject based on the ideXlab platform.
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Expression and activity of cocaine- and Amphetamine-Regulated Transcript peptide1–39 in the rat
Regulatory Peptides, 2006Co-Authors: Siok L. Dun, Jun Yang, Jaw Kang Chang, Eugen Brailoiu, Wei-kung Hsieh, Chih-chia Lai, Nae J. DunAbstract:Abstract Cocaine- and Amphetamine-Regulated Transcript (CART) peptide consists of a family of peptides. Expression of the peptide fragment CART1–39 was explored in the rat using an antiserum directed against CART1–39 of the short form of the human CART prohormone. CART1–39-immunoreactivity, herein referred to as irCART, was detected in the rat central and peripheral nervous tissues with a pattern similar to that labeled with the antiserum CART55–102 or CART79–102. For example, irCART cells were detected in the hypothalamus, pons, medulla oblongata, spinal cord, and adrenal medulla. In urethane-anesthetized rats, CART1–39 (0.05 to 2 nmol) by intrathecal injection did not cause a significant change of blood pressure or heart rate, but potentiated the pressor effects of glutamate injected intrathecally. Lastly, the effect of CART1–39 on intracellular calcium concentrations [Ca2+]i was assessed and compared to that caused by CART55–102 in cultured rat cortical neurons using the microfluorimetric method. CART1–39 (100 nM) induced two types of responses in a population of cortical neurons: 1) a slowly rising increase in [Ca2+]i superimposed with oscillations, and 2) a fast increase followed by a sustained increase of [Ca2+]i. CART55–102 caused only a slowly rising increase in [Ca2+]i in cortical neurons. Our result shows that the expression pattern of irCART in the rat nervous system and the potentiating action of CART1–39 on glutamate-induced pressor response is similar to that reported for CART55–102; but the calcium mobilizing action of CART1–39 differs from that of CART55–102, suggesting the possible existence of multiple CART receptors coupled to different calcium signaling pathways.
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Cocaine- and Amphetamine-Regulated Transcript peptide and sympatho-adrenal axis.
Peptides, 2006Co-Authors: Siok L. Dun, G. Cristina Brailoiu, Jun Yang, Jaw Kang Chang, Nae J. DunAbstract:Cocaine- and Amphetamine-Regulated Transcript peptide (CART) is constitutively expressed in discrete regions of the mammalian central and peripheral nervous system. Immunohistochemical studies reveal a well-defined network of CART-immunoreactive (irCART) neurons organized along the sympatho-adrenal axis. Sympathetic preganglionic neurons, but not parasympathetic preganglionic neurons, in the lateral horn area are CART-positive; which in turn innervate postganglionic neurons in the paravertebral and prevertebral sympathetic ganglia as well as the adrenal medulla. A population of chromaffin cells in the adrenal medulla is CART-positive; whereas, postganglionic neurons are not. Sympathetic preganglionic neurons themselves are contacted by irCART cell processes arising from neurons in the arcuate nucleus, the retrochiasmatic nucleus and the rostral ventrolateral medulla. Results from several recent studies suggest CART directly excites neurons along the sympathetic neural axis or indirectly by potentiating the action of glutamate on NMDA receptors, as evidenced by an elevation of blood pressure and heart rate following intracerebroventricular, intracisternal or intrathecal administration of the peptide to anesthetized rats or conscious rabbits.
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Differential expression of cocaine- and Amphetamine-Regulated Transcript-immunoreactivity in the rat spinal preganglionic nuclei
Neuroscience letters, 2000Co-Authors: Siok L. Dun, Jun Yang, Nae J. Dun, Deoclécio A. Chianca, Jaw Kang ChangAbstract:The distribution of cocaine- and Amphetamine-Regulated Transcript-like immunoreactivity (CART-LI) was investigated in the rat spinal cords with the use of an antiserum against the CART peptide fragment 55-102. CART-LI fibers were concentrated in the superficial layers of the dorsal horn of all segments. In addition to CART-LI fibers, intensely labeled somata were detected in the intermediolateral cell column (IML) and other sympathetic preganglionic nuclei of the thoracolumbar segments. In the lumbosacral segments, CART-LI fibers but not somata were seen in the sacral parasympathetic nucleus. Double-labeling the spinal sections with choline acetyltransferase (ChAT)-antisera and CART-antisera revealed that the large majority of ChAT-positive somata in the sympathetic preganglionic nuclei were CART-positive, whereas ChAT-positive somata in the parasympathetic preganglionic nuclei were CART-negative. Our results show that CART-LI is selectively expressed in a population of sympathetic preganglionic neurons (SPNs), but not in parasympathetic preganglionic neurons (PPNs) of the rat.
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Cocaine- and Amphetamine-Regulated Transcript-immunoreactivity in the rat sympatho-adrenal axis.
Neuroscience letters, 2000Co-Authors: Nae J. Dun, Siok L. Dun, Jun Yang, Ernest H. Kwok, Jaw Kang ChangAbstract:Distribution of cocaine- and Amphetamine-Regulated Transcript-like immunoreactivity (CART-LI) was studied in the rat spinal cord, sympathetic ganglia and adrenal glands by immunohistochemical methods, utilizing a polyclonal antiserum raised against the CART peptide fragment 55-102. CART-LI was detected in nerve fibers and in basket-like terminals surrounding many postganglionic neurons of the superior cervical ganglion (SCG), stellate, paravertebral and prevertebral ganglia. Postganglionic neurons exhibited low or non-detectable levels of CART-LI. Surgical sectioning of the cervical sympathetic trunk for 6-7 days resulted in a nearly complete loss of CART-LI fibers and terminals in the SCG. In the adrenal gland, CART-LI nerve fibers formed a plexus underneath the capsule, some of which bifurcated and made a sharp turn toward the adrenal medulla, where clusters of chromaffin cells were intensely labeled. The detection of CART-LI in sympathetic ganglia and adrenal glands extends the previous observation of the presence of CART-LI in sympathetic preganglionic neurons and further supports the notion that CART peptide(s) may function as a signaling molecule in the sympatho-adrenal axis.
Siok L. Dun - One of the best experts on this subject based on the ideXlab platform.
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Expression and activity of cocaine- and Amphetamine-Regulated Transcript peptide1–39 in the rat
Regulatory Peptides, 2006Co-Authors: Siok L. Dun, Jun Yang, Jaw Kang Chang, Eugen Brailoiu, Wei-kung Hsieh, Chih-chia Lai, Nae J. DunAbstract:Abstract Cocaine- and Amphetamine-Regulated Transcript (CART) peptide consists of a family of peptides. Expression of the peptide fragment CART1–39 was explored in the rat using an antiserum directed against CART1–39 of the short form of the human CART prohormone. CART1–39-immunoreactivity, herein referred to as irCART, was detected in the rat central and peripheral nervous tissues with a pattern similar to that labeled with the antiserum CART55–102 or CART79–102. For example, irCART cells were detected in the hypothalamus, pons, medulla oblongata, spinal cord, and adrenal medulla. In urethane-anesthetized rats, CART1–39 (0.05 to 2 nmol) by intrathecal injection did not cause a significant change of blood pressure or heart rate, but potentiated the pressor effects of glutamate injected intrathecally. Lastly, the effect of CART1–39 on intracellular calcium concentrations [Ca2+]i was assessed and compared to that caused by CART55–102 in cultured rat cortical neurons using the microfluorimetric method. CART1–39 (100 nM) induced two types of responses in a population of cortical neurons: 1) a slowly rising increase in [Ca2+]i superimposed with oscillations, and 2) a fast increase followed by a sustained increase of [Ca2+]i. CART55–102 caused only a slowly rising increase in [Ca2+]i in cortical neurons. Our result shows that the expression pattern of irCART in the rat nervous system and the potentiating action of CART1–39 on glutamate-induced pressor response is similar to that reported for CART55–102; but the calcium mobilizing action of CART1–39 differs from that of CART55–102, suggesting the possible existence of multiple CART receptors coupled to different calcium signaling pathways.
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Cocaine- and Amphetamine-Regulated Transcript peptide and sympatho-adrenal axis.
Peptides, 2006Co-Authors: Siok L. Dun, G. Cristina Brailoiu, Jun Yang, Jaw Kang Chang, Nae J. DunAbstract:Cocaine- and Amphetamine-Regulated Transcript peptide (CART) is constitutively expressed in discrete regions of the mammalian central and peripheral nervous system. Immunohistochemical studies reveal a well-defined network of CART-immunoreactive (irCART) neurons organized along the sympatho-adrenal axis. Sympathetic preganglionic neurons, but not parasympathetic preganglionic neurons, in the lateral horn area are CART-positive; which in turn innervate postganglionic neurons in the paravertebral and prevertebral sympathetic ganglia as well as the adrenal medulla. A population of chromaffin cells in the adrenal medulla is CART-positive; whereas, postganglionic neurons are not. Sympathetic preganglionic neurons themselves are contacted by irCART cell processes arising from neurons in the arcuate nucleus, the retrochiasmatic nucleus and the rostral ventrolateral medulla. Results from several recent studies suggest CART directly excites neurons along the sympathetic neural axis or indirectly by potentiating the action of glutamate on NMDA receptors, as evidenced by an elevation of blood pressure and heart rate following intracerebroventricular, intracisternal or intrathecal administration of the peptide to anesthetized rats or conscious rabbits.
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Cocaine- and Amphetamine-Regulated Transcript peptide attenuates phenylephrine-induced bradycardia in anesthetized rats.
American journal of physiology. Regulatory integrative and comparative physiology, 2003Co-Authors: Phouangmala Scruggs, Siok L. Dun, Nae J. DunAbstract:The present study was undertaken to investigate the origin of cocaine- and Amphetamine-Regulated Transcript (CART) peptide immunoreactive (irCART) fibers observed in the nucleus of the solitary tract (NTS) and assess the role of CART peptide on phenylephrine (PE)-induced baroreflex. Immunohistochemical and retrograde tract-tracing studies showed that some of the irCART fibers observed in the NTS may have their cell bodies in the nodose ganglia. In urethane-anesthetized rats, intracisternal or bilateral intra-NTS microinjection of the CART peptide fragment 55-102 (0.1-3 nmol), referred to herein as CARTp, consistently and dose dependently attenuated PE-induced bradycardia. CARTp, in the doses used here, caused no significant changes of resting blood pressure or heart rate. Bilateral intra-NTS injections of CART antibody (1:500) potentiated PE-induced bradycardia. Injections of saline, normal rabbit serum, or concomitant injection of CARTp and CART antiserum into the NTS caused no significant changes of PE-induced baroreflex. The result suggests that endogenously released CARTp from primary afferents or exogenously administered CARTp modulates PE-induced baroreflex.
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Differential expression of cocaine- and Amphetamine-Regulated Transcript-immunoreactivity in the rat spinal preganglionic nuclei
Neuroscience letters, 2000Co-Authors: Siok L. Dun, Jun Yang, Nae J. Dun, Deoclécio A. Chianca, Jaw Kang ChangAbstract:The distribution of cocaine- and Amphetamine-Regulated Transcript-like immunoreactivity (CART-LI) was investigated in the rat spinal cords with the use of an antiserum against the CART peptide fragment 55-102. CART-LI fibers were concentrated in the superficial layers of the dorsal horn of all segments. In addition to CART-LI fibers, intensely labeled somata were detected in the intermediolateral cell column (IML) and other sympathetic preganglionic nuclei of the thoracolumbar segments. In the lumbosacral segments, CART-LI fibers but not somata were seen in the sacral parasympathetic nucleus. Double-labeling the spinal sections with choline acetyltransferase (ChAT)-antisera and CART-antisera revealed that the large majority of ChAT-positive somata in the sympathetic preganglionic nuclei were CART-positive, whereas ChAT-positive somata in the parasympathetic preganglionic nuclei were CART-negative. Our results show that CART-LI is selectively expressed in a population of sympathetic preganglionic neurons (SPNs), but not in parasympathetic preganglionic neurons (PPNs) of the rat.
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Cocaine- and Amphetamine-Regulated Transcript-immunoreactivity in the rat sympatho-adrenal axis.
Neuroscience letters, 2000Co-Authors: Nae J. Dun, Siok L. Dun, Jun Yang, Ernest H. Kwok, Jaw Kang ChangAbstract:Distribution of cocaine- and Amphetamine-Regulated Transcript-like immunoreactivity (CART-LI) was studied in the rat spinal cord, sympathetic ganglia and adrenal glands by immunohistochemical methods, utilizing a polyclonal antiserum raised against the CART peptide fragment 55-102. CART-LI was detected in nerve fibers and in basket-like terminals surrounding many postganglionic neurons of the superior cervical ganglion (SCG), stellate, paravertebral and prevertebral ganglia. Postganglionic neurons exhibited low or non-detectable levels of CART-LI. Surgical sectioning of the cervical sympathetic trunk for 6-7 days resulted in a nearly complete loss of CART-LI fibers and terminals in the SCG. In the adrenal gland, CART-LI nerve fibers formed a plexus underneath the capsule, some of which bifurcated and made a sharp turn toward the adrenal medulla, where clusters of chromaffin cells were intensely labeled. The detection of CART-LI in sympathetic ganglia and adrenal glands extends the previous observation of the presence of CART-LI in sympathetic preganglionic neurons and further supports the notion that CART peptide(s) may function as a signaling molecule in the sympatho-adrenal axis.
Stephen R. Bloom - One of the best experts on this subject based on the ideXlab platform.
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Elevated cocaine- and Amphetamine-Regulated Transcript immunoreactivity in the circulation of patients with neuroendocrine malignancy.
The Journal of clinical endocrinology and metabolism, 2008Co-Authors: Paul Bech, Kevin G Murphy, Virginia Winstanley, Amir H Sam, Karim Meeran, Mohammad A. Ghatei, Stephen R. BloomAbstract:Context: Cocaine- and Amphetamine-Regulated Transcript (CART) codes for a peptide widely distributed in nervous and endocrine tissues. CART immunoreactivity (CART-LI) has been detected in human insulinomas. Objective: The objective of the study was to investigate the measurement of plasma CART-LI as a tumor marker of neuroendocrine malignancy. Design and Subjects: Plasma CART-LI levels were measured in 401 patients with a range of diagnoses: neuroendocrine malignancy (n = 131), after removal of neuroendocrine malignancy (n = 27), without any form of tumor or renal impairment (n = 192), with renal impairment (n = 17) and with nonneuroendocrine tumors (n = 34). Chromatography methods were used to investigate CART-LI circulating in human plasma. Results: The upper limit of normal calculated for CART-LI was 150 pmol/liter. Mean circulating plasma CART-LI among neuroendocrine tumor patients was 440 pmol/liter, 56% of subjects having levels greater than 150 pmol/liter. Measuring CART-LI in addition to chromogra...
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Regulation of rat pituitary cocaine- and Amphetamine-Regulated Transcript (CART) by CRH and glucocorticoids.
American journal of physiology. Endocrinology and metabolism, 2004Co-Authors: Sarah Stanley, Kevin Murphy, M A Ghatei, Gavin A. Bewick, May Kong, Jolanta Opacka-juffry, Jv Gardiner, Caroline Jane Small, Stephen R. BloomAbstract:Cocaine- and Amphetamine-Regulated Transcript (CART) was originally isolated from rat brain, but CART is also synthesized and stored in the anterior pituitary. The localization of pituitary CART an...
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A role for arcuate cocaine and Amphetamine-Regulated Transcript in hyperphagia, thermogenesis, and cold adaptation
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2003Co-Authors: May Kong, Caroline R Abbott, Kevin Murphy, M A Ghatei, Sarah Stanley, James V. Gardiner, Asha Seth, Ian P. Connoley, David A. Stephens, Stephen R. BloomAbstract:SPECIFIC AIMSThe hypothalamic neuropeptide cocaine and Amphetamine-Regulated Transcript (CART) was originally reported to act as an anorectic peptide; however, we have shown that direct injection o...
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Quantification and synthesis of cocaine- and Amphetamine-Regulated Transcript peptide (79-102)-like immunoreactivity and mRNA in rat tissues.
The Journal of endocrinology, 2000Co-Authors: K. G. Murphy, Michael J Kuhar, Caroline R Abbott, Michela Rossi, M A Ghatei, Sarah Stanley, James V. Gardiner, M. Mahmoudi, Richard G. Hunter, Stephen R. BloomAbstract:The distribution of cocaine- and Amphetamine-Regulated Transcript peptide (79-102)-like immunoreactivity (CART-LI) was quantified in brain and peripheral tissues of male and female Wistar rats, and male obese (fa/fa) and heterozygous (Fa/+) Zucker rats using a specific RIA. CART-LI tissue levels have not been quantified previously. The assay, using cocaine- and Amphetamine-Regulated Transcript (CART) (79-102) as a standard and radioactive tracer and an antibody to CART (79-102) fragment, detected CART-LI in all brain regions examined, the anterior and posterior pituitary, the spinal cord and throughout the gastrointestinal tract of both male and female Wistar rats. The highest concentrations were found in the hypothalamus, duodenum, anterior pituitary and posterior pituitary (50.6+/-4.4, 26.1+/-4.2, 50.0+/-1.3 and 373.0+/-55.2 pmol/g wet tissue respectively, means+/- s.e.m., n=6-10 male animals). There was no significant variation between the sexes. The concentrations of CART-LI in hypothalami and anterior and posterior pituitaries from fa/fa rats were significantly (P
