Structural domains determining signalling characteristics of the CRH-receptor type 1 variant R1β and response to PKC phosphorylation

2008 ◽  
Vol 20 (1) ◽  
pp. 40-49 ◽  
Author(s):  
Thalia Teli ◽  
Danijela Markovic ◽  
Margaret E. Hewitt ◽  
Michael A. Levine ◽  
Edward W. Hillhouse ◽  
...  
Keyword(s):  
Receptor Type ◽  
Structural Domains ◽  
Crh Receptor Type 1

scholarly journals Regulation des Angstverhaltens — zur Rolle neuronaler Netzwerke

BIOspektrum ◽  
2019 ◽  
Vol 25 (7) ◽  
pp. 711-714
Author(s):  
Nina Dedic ◽  
Jan M. Deussing
Keyword(s):  
Stress Response ◽  
Ventral Tegmental Area ◽  
Long Range ◽  
Dopamine Release ◽  
Receptor Type ◽  
Projection Neurons ◽  
Neuronal Circuit ◽  
Brain Reward ◽  
Crh Receptor Type 1

AbstractThe corticotropin-releasing hormone (CRH) system orchestrates the organism’s stress response including the regulation of adaptive be haviours. Here we describe a novel neuronal circuit, which acts anxiety suppressing and positively modulates dopamine release. This anxiolytic circuit comprises inhibitory CRH-expressing, long-range projection neurons within the extended amygdala. These neurons innervate the ventral tegmental area, a prominent brain reward center that expresses high levels of CRH receptor type 1.

scholarly journals CRH Acts on CRH-R1 and -R2 to Differentially Modulate the Expression of Large-Conductance Calcium-Activated Potassium Channels in Human Pregnant Myometrium

Endocrinology ◽  
2011 ◽  
Vol 152 (11) ◽  
pp. 4406-4417 ◽  
Author(s):  
Chen Xu ◽  
Lu Gao ◽  
Xingji You ◽  
Ling Dai ◽  
Yuan Li ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Receptor Type ◽  
Uterine Contractility ◽  
Myometrial Cells ◽  
Calcium Activated Potassium Channels ◽  
Spontaneous Contractions ◽  
Crh Receptor Type 1 ◽  
Interfering Rna

CRH has been implicated to play a key role in the control of human pregnancy and parturition. Large-conductance potassium channels (BKCa) play a pivotal role in the modulation of uterine contractility during pregnancy. The objectives of the present study were to investigate the effect of CRH on BKCa expression in human pregnant myometrial cells. Myometrial tissues were collected at cesarean section from pregnant women not-in-labor (TNL) or in-labor (TL) at term, and myocytes were isolated and cultured. CRH was identified in human pregnant myometrium and mainly expressed in myometrial myocytes. Cultured myometrial cells were able to secrete CRH. In TNL myometrial cells, CRH treatment increased the expression of BKCa α- and β-subunits. CRH receptor type 1 (CRH-R1) antagonist, antalarmin, decreased whereas CRH receptor type 2 (CRH-R2) antagonist, astressin2b, increased the expression of BKCa. CRH-R2 small interfering RNA (siRNA) caused an increase, but CRH-R1 siRNA resulted in a decrease, in BKCa expression. In contrast to TNL cells, CRH exhibited an opposite effect on BKCa expression in TL myometrial cells, i.e. decreased BKCa expression. Antalarmin enhanced but astressin2b reduced BKCa expression. CRH-R2 siRNA decreased whereas CRH-R1 siRNA increased BKCa expression. 1,3-Dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one significantly inhibited the frequency of spontaneous contractions of myometrial strips, and this effect was significantly decreased in TL strips compared with TNL ones. Our data suggest that CRH-R1 and CRH-R2 show differential regulation of BKCa expression. These effects mediated by CRH-R1 and CRH-R2 are changed after the onset of labor. This leads us to suggest that CRH may fine-tune myometrial contractility by modulating the expression of BKCa during pregnancy and labor.

scholarly journals Regulation of Estradiol and Progesterone Production by CRH-R1 and -R2 Is through Divergent Signaling Pathways in Cultured Human Placental Trophoblasts

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4918-4928 ◽  
Author(s):  
Lu Gao ◽  
Yi Tao ◽  
Tianxiao Hu ◽  
Weina Liu ◽  
Chen Xu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Phospholipase C ◽  
Culture Media ◽  
Receptor Type ◽  
Kinase C ◽  
Protein Kinase C Inhibitor ◽  
Crh Receptor Type 1 ◽  
Gαi Protein

Abstract CRH and its related peptides urocortins (UCN) have been identified in placenta and implicated to play pivotal roles in the regulation of pregnancy and parturition in humans. The objectives of present study were to investigate the effects of endogenous CRH and its related peptides in the regulation of steroid production in placenta. Placental trophoblasts were isolated from term placenta tissues and cultured for 72 h. Estradiol (E2) and progesterone (P4) contents in culture media were determined by radioimmunoassay. Treatment of cultured trophoblasts with CRH or UCNI antibody showed decreased E2, whereas increased P4 production. Treatment of cells with CRH receptor type 1 antagonist antalarmin or CRH receptor type 2 (CRH-R2) antagonist astressin-2b also decreased E2 but increased P4 production. Knockdown of CRH receptor type 1 or CRH-R2 cells showed a decrease in E2 production and an increase in P4 production. In CRH-R2 knockdown cells, CRH stimulated GTP-bound Gαs protein and phosphorylated phospholipase C-β3. Adenylyl cyclase and protein kinase A inhibitors blocked CRH-induced increased E2 production but not decreased P4 production. PLC inhibitor U73122 and protein kinase C inhibitor chelerythrine blocked the effects of CRH on E2 and P4 production in CRH-R2 knockdown cells. UCNIII, the specific CRH-R2 agonist, stimulated GTP-bound Gαi protein and phosphorylated phospholipase C-β3 expression. Both U73122 and chelerythrine blocked UCNIII-induced increased E2 production and decreased P4 production. We suggest that CRH and its related peptides might be involved in changes in the progesterone to estrogen ratio during human pregnancy.

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