Handbook of experimental pharmacology
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Handb Exp Pharmacol · Jan 2009
ReviewCough sensors. V. Pharmacological modulation of cough sensors.
Several airway afferent nerve subtypes have been implicated in coughing. These include bronchopulmonary C-fibers, rapidly adapting airway mechanoreceptors and touch-sensitive tracheal Adelta-fibers (also called cough receptors). ⋯ In this review we catalogue the chemical agents that stimulate and/or modulate the activity of the airway afferent nerves involved in cough, and describe the specific mechanisms involved in these effects. In addition, we describe the mechanisms of action of a number of chemical inhibitors of these afferent nerve subtypes, and attempt to relate this information to the regulation of coughing in health and disease.
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Handb Exp Pharmacol · Jan 2009
ReviewSkin aquaporins: function in hydration, wound healing, and skin epidermis homeostasis.
Several aquaporins (AQPs) are expressed in mammalian skin. Some are directly involved in water transport, such as AQP5, which is involved in sweat secretion. In contrast, the physiological role of skin aquaglyceroporins, which permeate both water and glycerol, appears more and more complex. ⋯ Both water and glycerol transport by AQP3 appear to play an important role in hydration of mammalian skin epidermis. In addition, recent data suggest that glycerol transport by AQP3 is involved in the metabolism of lipids in skin as well as in the regulation of proliferation and differentiation of keratinocytes. Finally, AQP3 is also believed to be important in wound healing, as a water channel by facilitating cell migration, and as a glycerol transporter by enhancing keratinocyte proliferation and differentiation.
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Adenosine (Ado) regulates diverse cellular functions in the lung through its local production, release, metabolism, and subsequent stimulation of G-protein-coupled P1 purinergic receptors. The A(2B) adenosine receptor (A(2B)AR) is the predominant P1 purinergic receptor isoform expressed in surface airway epithelia, and Ado is an important regulator of airway surface liquid (ASL) volume through its activation of the cystic fibrosis transmembrane conductance regulator (CFTR). Through a delicate balance between sodium (Na(+)) absorption and chloride (Cl(-)) secretion, the ASL volume is optimized to promote ciliary activity and mucociliary clearance, effectively removing inhaled particulates. ⋯ Adenosine triphosphate (ATP) also regulates transepithelial Cl(-) conductance, but through a separate system that relies on stimulation of P2Y(2) purinergic receptors, mobilization of intracellular calcium, and activation of calcium-activated chloride channels (CaCCs). These pathways remain functional in CF, and may serve a protective role in the disease. In this chapter, we will review our current understanding of how Ado and related nucleotides regulate CFTR and Cl(-) conductance in the human airway, including the regulation of additional intracellular and extracellular signaling pathways that provide important links between ion transport and inflammation relevant to the disease.
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Pharmacotherapy can provide effective treatment of tobacco dependence and withdrawal, and thereby facilitate efforts to achieve and sustain tobacco abstinence. Currently approved medications for smoking cessation are nicotine replacement medications (NRT), including nicotine patch, gum, lozenge, sublingual tablet, inhaler and nasal spray, the antidepressant bupropion, and the nicotinic partial agonist varenicline. This review discusses the pharmacological basis for the use of these medications, and the properties that might contribute to their efficacy, safety, and abuse liability. The review also discusses how pharmacological principles can be used to improve existing medications, as well as assist in the development of new medications.
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Handb Exp Pharmacol · Jan 2009
ReviewCough sensors. II. Transient receptor potential membrane receptors on cough sensors.
The transient receptor potential (TRP) family of channels is represented by at least six members in primary sensory neurons. These include the TRP vanilloid subtypes 1 (TRPV1), 2, 3, and 4, the cold and menthol receptor TRPM8, and TRPA1. ⋯ Evidence in experimental animals and in patients with airway diseases indicates a marked hypersensitivity to cough induced by TRPV1 agonists. Recent studies with newly developed high-affinity and selective TRPV1 antagonists have revealed that TRPV1 inhibition reduces cough induced by citric acid or antigen challenge.