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AT1 receptors as mechanosensors
Michael Mederos y Schnitzler1, Ursula Storch, Thomas Gudermann
1Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilians University of Munich, Goethestr. 33, 80336 Munich, Germany. mederos@lrz.uni-muenchen.de
Current Opinion in Pharmacology
|December 15, 2010
Summary
G-protein-coupled receptors, initially known for signaling, are now recognized as crucial mechanosensors. This discovery reveals their role in mechanical sensing and physiological processes like vasoconstriction.
Area of Science:
- Biochemistry
- Cell Biology
- Physiology
Background:
- G-protein-coupled receptors (GPCRs) are key in neurohormonal signaling.
- Emerging evidence suggests GPCRs also function in mechanotransduction.
- The angiotensin II AT(1) receptor was the first GPCR identified as a mechanosensor.
Purpose of the Study:
- To explore the role of GPCRs in mechanotransduction.
- To investigate the mechanical sensitivity of various GPCRs, including G(q/11) and G(i/o)-coupled receptors.
- To understand the mechanism and physiological relevance of mechanically induced GPCR activation.
Main Methods:
- Review of existing literature on GPCRs and mechanotransduction.
- Analysis of studies identifying GPCRs as mechanosensors.
- Examination of evidence for agonist-independent receptor activation via conformational changes.
Main Results:
- Several G(q/11)-coupled receptors are sensitive to mechanical stimuli.
- Initial evidence indicates G(i/o)-coupled receptors are also susceptible to mechanical stimulation.
- Mechanical activation is agonist-independent, involving distinct conformational changes.
Conclusions:
- GPCRs are versatile receptors involved in both chemical and mechanical signaling.
- Mechanically induced GPCR activation has physiological roles, including myogenic vasoconstriction.
- This mechanism is implicated in the pathogenesis of cardiac hypertrophy.
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