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GPCRs and Arrestins in Airways: Implications for Asthma

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Arrestins - Pharmacology and Therapeutic Potential

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 219))

Abstract

The obstructive lung disease asthma is treated by drugs that target, either directly or indirectly, G protein-coupled receptors (GPCRs). GPCRs coupled to Gq are the primary mediators of airway smooth muscle (ASM) contraction and increased airway resistance, whereas the Gs-coupled beta-2-adrenoceptor (β2AR) promotes pro-relaxant signaling in and relaxation of ASM resulting in greater airway patency and reversal of life-threatening bronchoconstriction. In addition, GPCR-mediated functions in other cell types, including airway epithelium and hematopoietic cells, are involved in the control of lung inflammation that causes most asthma. The capacity of arrestins to regulate GPCR signaling, via either control of GPCR desensitization/resensitization or G protein-independent signaling, renders arrestins an intriguing therapeutic target for asthma and other obstructive lung diseases. This review will focus on the potential role of arrestins in those GPCR-mediated airway cell functions that are dysregulated in asthma.

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Acknowledgments

Work in the authors’ lab is funded by HL58506, P01 HL114471 (RBP), HL93013 (RBP and JKLW), HL084123 (JKLW), and AI079236 (JKLW and RAB).

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Authors and Affiliations

  1. Center for Translational Medicine, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, 1025 Walnut Street, Suite 317, Philadelphia, PA, 19107, USA

    Raymond B. Penn

  2. Department of Pharmacology and Pharmaceutical Sciences, University of Houston, Houston, TX, USA

    Richard A. Bond

  3. Department of Medicine, Duke University Medical Center, Durham, NC, USA

    Julia K. L. Walker

Authors
  1. Raymond B. Penn
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  2. Richard A. Bond
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  3. Julia K. L. Walker
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Correspondence to Raymond B. Penn .

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Editors and Affiliations

  1. Professor of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

    Vsevolod V. Gurevich

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Penn, R.B., Bond, R.A., Walker, J.K.L. (2014). GPCRs and Arrestins in Airways: Implications for Asthma. In: Gurevich, V. (eds) Arrestins - Pharmacology and Therapeutic Potential. Handbook of Experimental Pharmacology, vol 219. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-41199-1_20

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