Last update 01 Nov 2024

CALCR x LEPR

Last update 01 Nov 2024

Basic Info

Related Targets

CALCRLEPR

Drugs associated with CALCR x LEPR

Metreleptin/Pramlintide Acetate

Target

CALCR x LEPR

Mechanism

CALCR agonists [+1]

Active Org.-

Originator Org.

Bristol Myers Squibb Co. /Saint Nazaire Assets/

Active Indication-

Inactive Indication

Obesity

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CALCR x LEPR

100 Translational Medicine associated with CALCR x LEPR

0 Patents (Medical) associated with CALCR x LEPR

Literatures (Medical) associated with CALCR x LEPR

01 Oct 2018·American Journal of Physiology-Regulatory, Integrative and Comparative PhysiologyQ2 · MEDICINE

Rodent models of leptin receptor deficiency are less sensitive to amylin

Q2 · MEDICINE

Article

Author: Boyle, Christina N. ; Lutz, Thomas A. ; Duffy, Sonya

The pancreatic hormone amylin is released from beta cells following nutrient ingestion and contributes to the control of body weight and glucose homeostasis. Amylin reduces food intake by activating neurons in the area postrema (AP). Amylin was also shown to synergize with the adipokine leptin, with combination therapy producing greater weight loss and food intake reduction than either hormone alone. Although amylin and leptin were initially thought to interact downstream of the AP in the hypothalamus, recent findings show that the two hormones can act on the same AP neurons, suggesting a more direct relationship. The objective of this study was to determine whether amylin action depends on functional leptin signaling. We tested the ability of amylin to induce satiation and to activate its primary target neurons in the AP in two rodent models of LepR deficiency, the db/db mouse and the Zucker diabetic fatty (ZDF) rat. When compared with wild-type (WT) mice, db/db mice exhibited reduced amylin-induced satiation, reduced amylin-induced Fos in the AP, and a lower expression of calcitonin receptor (CTR) protein, the core component of all amylin receptors. ZDF rats also showed no reduction in food intake following amylin treatment; however, unlike the db/db mice, levels of amylin-induced Fos and CTR in the AP were no different than WT rats. Our results suggest that LepR expression is required for the full anorexic effect of amylin; however, the neuronal activation in the AP seems to depend on the type of LepR mutation.

01 Mar 2016·European Journal of NeuroscienceQ3 · MEDICINE

Amylin receptor components and the leptin receptor are co‐expressed in single rat area postrema neurons

Q3 · MEDICINE

Article

Author: Liberini, Claudia G. ; Hope, Bruce T. ; Cifani, Carlo ; Lutz, Thomas A. ; Venniro, Marco ; Boyle, Christina N.

AbstractAmylin is a pancreatic β‐cell hormone that acts as a satiating signal to inhibit food intake by binding to amylin receptors (AMYs) and activating a specific neuronal population in the area postrema (AP). AMYs are heterodimers that include a calcitonin receptor (CTR) subunit [CTR isoform a or b (CTRa or CTRb)] and a member of the receptor activity‐modifying proteins (RAMPs). Here, we used single‐cell quantitative polymerase chain reaction to assess co‐expression of AMY subunits in AP neurons from rats that were injected with amylin or vehicle. Because amylin interacts synergistically with the adipokine leptin to reduce body weight, we also assessed the co‐expression of AMY and the leptin receptor isoform b (LepRb) in amylin‐activated AP neurons. Single cells were collected from Wistar rats and from transgenic Fos‐GFP rats that express green fluorescent protein (GFP) under the control of the Fos promoter. We found that the mRNAs of CTRa, RAMP1, RAMP2 and RAMP3 were all co‐expressed in single AP neurons. Moreover, most of the CTRa+ cells co‐expressed more than one of the RAMPs. Amylin down‐regulated RAMP1 and RAMP3 but not CTR mRNAs in AMY+ neurons, suggesting a possible negative feedback mechanism of amylin at its own primary receptors. Interestingly, amylin up‐regulated RAMP2 mRNA. We also found that a high percentage of single cells that co‐expressed all components of a functional AMY expressed LepRb mRNA. Thus, single AP cells expressed both AMY and LepRb, which formed a population of first‐order neurons that presumably can be directly activated by amylin and, at least in part, also by leptin.

01 Nov 2015·Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology

Leptin receptor of the hind brain nuclei is involved in the conditioned taste preference of rats.

Article

Author: Lin, Cai-xia ; Yan, Jian-qun ; Kang, Yu-ming ; Chen, Ke ; Zhang, Shao-yun ; Luo, Xiao ; Sun, Bo

OBJECTIVEConditioned taste preference (CTP) is a taste learning reflex by which an animal learns to prefer a substance which tastes not well and has been studied with much interest in recent years. However, the neural substrates of CTP are less known. This study aimed to determine the possible neural path- ways of CTP and whether serum leptin level and the leptin receptor (OB-Rb) in the hind brain are involved following CTP formation.METHODSWe established CTP of quinine in rats with a 2-bottle preference test. The serum leptin concentrations were detected, the expression of c-fos in the rat brain was tested to determine the nuclei in relation with establishment of CTR Finally, the OB-Rb mRNA expression was examined by RT-qPCR assay in parabrachial nucleus (PBN) and the nucleus of the solitary tract (NST) of the hind brain.RESULTSCompared with control group, the level of serum leptin was higher in the CTP group (4.58 ± 0.52 vs 1.67 ± 0.25 µg/L, P < 0.01); increased c-fos positive cells were found in the anterior hypothalamus (AH, 221.75 ± 4.96 vs. 178.50 ± 6.63 cells/mm², P < 0.05), the basal lateral amygdala (BLA, 70.75 ± 6.17 vs 56.50 ± 3.62 cells/ mm², P < 0.05) and the nucleus of the solitary tract (NST, 41.25 ± 1.32 vs 32.50 ± 1.02 cells/mm², P < 0.05). But in ventromedial nucleus of the hypothalamus (VMH, 20.75 ± 2.73 vs 38.5 ± 1.54 per 1 mm², P < 005), PBN (21.50 ± 2.24 vs 36.25 ± 1.49 cells/mm², P < 0.05) and the central nucleus of the amygdala (CeA, 22.25 ± 1.53 vs 35.50 ± 2.11 cells/mm², P < 0.05), the number of c-fos positive cells was decreased in the CTP group. In addition, we found OB-Rb mRNA expression in PBN of CTP group rats was higher than that of control group (0.95 ± 0.055 vs 0.57 ± 0.034, P < 0.05), while there was no significant difference of OB-Rb mRNA expression in NST between the two groups.CONCLUSIONNuclei AH, BLA, NST, VMH, PBN and CeA participate in the formation of CTP. Leptin and its receptor in PBN may be involved in the formation and maintenance of CTP.

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