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GHS-R1a constitutive activity and its physiological relevance
- Source :
- Frontiers in Neuroscience, Vol 7 (2013)
- Publication Year :
- 2013
- Publisher :
- Frontiers Media S.A., 2013.
-
Abstract
- Abundant evidences have shown that ghrelin, by its binding to GHS-R1a, plays an important role for fundamental physiological functions. Increasing attention is given to the GHS-R1a unusually high constitutive activity and its contribution to downstream signalling and physiological processes. Here, we review recent lines of evidences showing that the interaction between ligand-binding pocket TM domains and the ECL2 could be partially responsible for this high constitutive activity. Interestingly, GHSR-1a constitutive activity activates in turn the downstream PLC, PKC and CRE signalling pathways and this activation is reversed by the inverse agonist [D-Arg1, D-Phe5, D-Trp7,9, Leu11]-substance P (MSP). Noteworthy, GHSR-1a exhibits a C-terminal-dependent constitutive internalization. Non-sense GHS-R1a mutation (Ala204Glu), first discovered in Moroccan patients, supports the role of GHSR-1a constitutive activity in physiological impairments. Ala204Glu-point mutation, altering exclusively the GHSR-1a constitutive activity, was associated with familial short stature syndrome. Altogether, these findings suggest that GHS-R1a constitutive activity could contribute to GH secretion or body weight regulation. Consequently, future research on basic and clinical applications of GHS-R1a inverse agonists will be challenging and potentially rewarding.
Details
- Language :
- English
- ISSN :
- 1662453X
- Volume :
- 7
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.4a87fa3283264daf841cf7c2701b24e0
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fnins.2013.00087