| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
and R2ß CRH Receptor Subtypes and Stimulation of Gq-Proteins
Sir Quinton Hazell Molecular Medicine Research Centre (D.K.G.,
H.S.R., E.S.K., E.W.H.) Department of Biological Sciences
University of Warwick Coventry, CV4 7AL, United Kingdom
The Johns Hopkins University School of Medicine Division of
Pediatric Endocrinology and the Ilyssa Centre for Cellular and
Molecular Endocrinology Department of Pediatrics Baltimore,
Maryland 21287
CRH and CRH-related peptides such as urocortin mediate their actions in the human myometrium via activation of two distinct classes of CRH receptors, R1 and R2. These heptahelical receptors are able to stimulate a number of different intracellular signals; one key mediator of G protein-activated intracellular signaling is the cascade of p42/p44, mitogen-activated protein kinase (MAPK). We therefore hypothesized that activation of MAPK might mediate CRH and or/urocortin actions in the myometrium.
In cultured human pregnant myometrial cells, urocortin but not CRH was
able to induce MAPK phosphorylation and activation, suggesting that in
the human myometrium these two peptides have distinct actions and
biological roles. To identify the particular receptor subtypes
mediating this phenomenon, all known CRH receptors present in the human
myometrial cells were stably expressed individually in HEK293 and CHO
cells, and their ability to activate MAPK was tested. The R1
and
R2ß, but not the R1ß, R1c, or R1d, receptor subtypes were able to
mediate urocortin-induced MAPK activation. The signaling components
were further investigated; activation of Gs, Go, or Gi proteins did not
appear to be involved, but activation of Gq with subsequent production
of inositol triphosphates (IP3) and protein
kinase C (PKC) activation correlated with MAPK phosphorylation. Studies
on Gq protein activation using
[-32P]-GTP-
-azidoanilide and
IP3 production in cells expressing the R1 or
R2ß CRH receptors demonstrated that urocortin was 10 times more
potent than CRH. Moreover, urocortin (UCN) generated peak responses
that were 50–70% greater than CRH in activating the Gq protein and
stimulating IP3 production.
In conclusion, UCN acting thought multiple receptor subtypes can stimulate myometrial MAPK via induction of the Gq/phospholipase C/IP3/PKC pathway, whereas CRH-induced activation of this pathway appears to be insufficient to achieve MAPK activation.
This article has been cited by other articles:
 |
|
 |
|
  D. Markovic, A. Punn, H. Lehnert, and D. K. Grammatopoulos Intracellular Mechanisms Regulating Corticotropin-Releasing Hormone Receptor-2{beta} Endocytosis and Interaction with Extracellularly Regulated Kinase 1/2 and p38 Mitogen-Activated Protein Kinase Signaling Cascades Mol. Endocrinol., March 1, 2008; 22(3): 689 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. V. Ivanova, R. Schubert, D. B. Duridanova, T. B. Bolton, L. T. Lubomirov, and H. S. Gagov Heart/Cardiac Muscle: Cocaine- and amphetamine-regulated transcript (CART) peptide as an in vivo regulator of cardiac function in Rana ridibunda frog Exp Physiol, November 1, 2007; 92(6): 1037 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Dan Jin, Ping He, Xingji You, Xiaoyan Zhu, Ling Dai, Qian He, Chunmin Liu, Ning Hui, Jinyan Sha, and Xin Ni Expression of Corticotropin-Releasing Hormone Receptor Type 1 and Type 2 in Human Pregnant Myometrium Reproductive Sciences, September 1, 2007; 14(6): 568 - 577. [Abstract] [PDF]
|
|
|
|
 |
|
 S. V. Wu, P.-q. Yuan, L. Wang, Y. L. Peng, C.-Y. Chen, and Y. Tache Identification and Characterization of Multiple Corticotropin-Releasing Factor Type 2 Receptor Isoforms in the Rat Esophagus Endocrinology, April 1, 2007; 148(4): 1675 - 1687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Punn, M. A. Levine, and D. K. Grammatopoulos Identification of Signaling Molecules Mediating Corticotropin-Releasing Hormone-R1{alpha}-Mitogen-Activated Protein Kinase (MAPK) Interactions: The Critical Role of Phosphatidylinositol 3-Kinase in Regulating ERK1/2 But Not p38 MAPK Activation Mol. Endocrinol., December 1, 2006; 20(12): 3179 - 3195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Breuiller-Fouche and G. Germain Gene and protein expression in the myometrium in pregnancy and labor. Reproduction, May 1, 2006; 131(5): 837 - 850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. W. Hillhouse and D. K. Grammatopoulos The Molecular Mechanisms Underlying the Regulation of the Biological Activity of Corticotropin-Releasing Hormone Receptors: Implications for Physiology and Pathophysiology Endocr. Rev., May 1, 2006; 27(3): 260 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Florio, M. Torricelli, L. Galleri, G. De Falco, E. Leucci, G. Calonaci, E. Picciolini, G. Ambrosini, E. A. Linton, and F. Petraglia High Fetal Urocortin Levels at Term and Preterm Labor J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5361 - 5365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Sooranna, N. Engineer, J. A. Z. Loudon, V. Terzidou, P. R. Bennett, and M. R. Johnson The Mitogen-Activated Protein Kinase Dependent Expression of Prostaglandin H Synthase-2 and Interleukin-8 Messenger Ribonucleic Acid by Myometrial Cells: The Differential Effect of Stretch and Interleukin-1{beta} J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3517 - 3527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Teli, D. Markovic, M. A. Levine, E. W. Hillhouse, and D. K. Grammatopoulos Regulation of Corticotropin-Releasing Hormone Receptor Type 1{alpha} Signaling: Structural Determinants for G Protein-Coupled Receptor Kinase-Mediated Phosphorylation and Agonist-Mediated Desensitization Mol. Endocrinol., February 1, 2005; 19(2): 474 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chen, M. Perrin, B. Brar, C. Li, P. Jamieson, M. DiGruccio, K. Lewis, and W. Vale Mouse Corticotropin-Releasing Factor Receptor Type 2{alpha} Gene: Isolation, Distribution, Pharmacological Characterization and Regulation by Stress and Glucocorticoids Mol. Endocrinol., February 1, 2005; 19(2): 441 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen and H. S. Randeva Genomic Organization of Mouse Orexin Receptors: Characterization of Two Novel Tissue-Specific Splice Variants Mol. Endocrinol., November 1, 2004; 18(11): 2790 - 2804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Peeters, H. W. Gohlmann, I. Van den Wyngaert, S. M. Swagemakers, L. Bijnens, S. U. Kass, and T. Steckler Transcriptional Response to Corticotropin-Releasing Factor in AtT-20 Cells Mol. Pharmacol., November 1, 2004; 66(5): 1083 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wietfeld, N. Heinrich, J. Furkert, K. Fechner, M. Beyermann, M. Bienert, and H. Berger Regulation of the Coupling to Different G Proteins of Rat Corticotropin-releasing Factor Receptor Type 1 in Human Embryonic Kidney 293 Cells J. Biol. Chem., September 10, 2004; 279(37): 38386 - 38394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Soloff, Y.-J. Jeng, M. Ilies, S. L. Soloff, M. G. Izban, T. G. Wood, N. I. Panova, G. V.N. Velagaleti, and G. D. Anderson Immortalization and characterization of human myometrial cells from term-pregnant patients using a telomerase expression vector Mol. Hum. Reprod., September 1, 2004; 10(9): 685 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Parham, S. Zervou, E. Karteris, R. D. Catalano, R. W. Old, and E. W. Hillhouse Promoter Analysis of Human Corticotropin-Releasing Factor (CRF) Type 1 Receptor and Regulation by CRF and Urocortin Endocrinology, August 1, 2004; 145(8): 3971 - 3983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. K. Brar, A. Chen, M. H. Perrin, and W. Vale Specificity and Regulation of Extracellularly Regulated Kinase1/2 Phosphorylation through Corticotropin-Releasing Factor (CRF) Receptors 1 and 2{beta} by the CRF/Urocortin Family of Peptides Endocrinology, April 1, 2004; 145(4): 1718 - 1729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Papadopoulou, J. Chen, H. S. Randeva, M. A. Levine, E. W. Hillhouse, and D. K. Grammatopoulos Protein Kinase A-Induced Negative Regulation of the Corticotropin-Releasing Hormone R1{alpha} Receptor-Extracellularly Regulated Kinase Signal Transduction Pathway: The Critical Role of Ser301 for Signaling Switch and Selectivity Mol. Endocrinol., March 1, 2004; 18(3): 624 - 639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Karteris, E. W. Hillhouse, and D. Grammatopoulos Urocortin II Is Expressed in Human Pregnant Myometrial Cells and Regulates Myosin Light Chain Phosphorylation: Potential Role of the Type-2 Corticotropin-Releasing Hormone Receptor in the Control of Myometrial Contractility Endocrinology, February 1, 2004; 145(2): 890 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Bayatti, J. Zschocke, and C. Behl Brain Region-Specific Neuroprotective Action and Signaling of Corticotropin-Releasing Hormone in Primary Neurons Endocrinology, September 1, 2003; 144(9): 4051 - 4060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Li, P. Chen, J. Vaughan, A. Blount, A. Chen, P. M. Jamieson, J. Rivier, M. S. Smith, and W. Vale Urocortin III Is Expressed in Pancreatic {beta}-Cells and Stimulates Insulin and Glucagon Secretion Endocrinology, July 1, 2003; 144(7): 3216 - 3224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Perrin, M. R. DiGruccio, S. C. Koerber, J. E. Rivier, K. S. Kunitake, D. L. Bain, W. H. Fischer, and W. W. Vale A Soluble Form of the First Extracellular Domain of Mouse Type 2beta Corticotropin-releasing Factor Receptor Reveals Differential Ligand Specificity J. Biol. Chem., April 25, 2003; 278(18): 15595 - 15600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Florio, L. Cobellis, J. Woodman, F. M. Severi, E. A. Linton, and F. Petraglia Levels of Maternal Plasma Corticotropin-Releasing Factor and Urocortin During Labor Reproductive Sciences, July 1, 2002; 9(4): 233 - 237. [Abstract] [PDF]
|
|
|
|
|
|
S. Zervou, E. Karteris, E.W. Hillhouse, and R.W. Old Steroids mediate the expression of cytoplasmic and membrane-linked components in human myometrial cells Mol. Hum. Reprod., July 1, 2002; 8(7): 597 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Dermitzaki, C. Tsatsanis, A. Gravanis, and A. N. Margioris Corticotropin-releasing Hormone Induces Fas Ligand Production and Apoptosis in PC12 Cells via Activation of p38 Mitogen-activated Protein Kinase J. Biol. Chem., March 29, 2002; 277(14): 12280 - 12287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Aggelidou, E. W. Hillhouse, and D. K. Grammatopoulos Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotropin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells PNAS, February 14, 2002; (2002) 52296399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. A. Pedersen, R. Wan, P. Zhang, and M. P. Mattson Urocortin, But Not Urocortin II, Protects Cultured Hippocampal Neurons from Oxidative and Excitotoxic Cell Death via Corticotropin-Releasing Hormone Receptor Type I J. Neurosci., January 15, 2002; 22(2): 404 - 412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. SLOMINSKI, J. WORTSMAN, A. PISARCHIK, B. ZBYTEK, E. A. LINTON, J. E. MAZURKIEWICZ, and E. T. WEI Cutaneous expression of corticotropin-releasing hormone (CRH), urocortin, and CRH receptors FASEB J, August 1, 2001; 15(10): 1678 - 1693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Aggelidou, E. W. Hillhouse, and D. K. Grammatopoulos Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotropin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells PNAS, March 5, 2002; 99(5): 3300 - 3305. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
