Handbook of experimental pharmacology
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Migraine is a neurovascular disorder which affects one fifth of the general population. Disability due to migraine is severe and involves patients from infancy through senescence and it is aggravated by the fact there is no complete cure. ⋯ These novel antagonists block the receptor for the sensory neuropeptide calcitonin gene-related peptide (CGRP), which upon release from peripheral terminals of trigeminal perivascular neurons dilates cranial arterial vessels. Whether neurogenic vasodilatation is the major contributing factor to generate the pain and the associated symptoms of the migraine attack or whether other sites of action of CGRP receptor antagonists are responsible for the antimigraine effect of these compounds is the subject of current and intense research.
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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
ReviewClinical cough II: therapeutic treatments and management of chronic cough.
Chronic cough is a common and frequently disruptive symptom which can be difficult to treat with currently available medicines. Asthma/eosinophilic airway disease and gastro-oesophageal reflux disease are most commonly associated with chronic cough but it may also trouble patients with chronic obstructive pulmonary disease, pulmonary fibrosis and lung cancer. Over the last three decades there have been a number of key advances in the clinical approach to cough and a number of international guidelines on the management of cough have been developed. ⋯ The main objective of new treatments for cough would be to identify ways to downregulate this heightened cough reflex but yet preserve its crucial role in protecting the airway. The combined efforts of clinicians, scientists and the pharmaceutical industry offer most hope for such a treatment breakthrough. The aim of this chapter is to provide some rationale for the current treatment recommendations and to offer some reflections on the management of patients with chronic cough.
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Handb Exp Pharmacol · Jan 2009
ReviewCough sensors. I. Physiological and pharmacological properties of the afferent nerves regulating cough.
The afferent nerves regulating cough have been reasonably well defined. The selective effects of general anesthesia on C-fiber-dependent cough and the opposing effects of C-fiber subtypes in cough have led to some uncertainty about their regulation of this defensive reflex. But a role for C-fibers in cough seems almost certain, given the unique pharmacological properties of these unmyelinated vagal afferent nerves and the ability of many C-fiber-selective stimulants to evoke cough. ⋯ These "cough receptors" are distinct from the slowly and rapidly adapting intrapulmonary stretch receptors responding to lung inflation. Indeed, intrapulmonary rapidly and slowly adapting receptors and pulmonary C-fibers may play no role or a nonessential role in cough, or might even actively inhibit cough upon activation. A critical review of the studies of the afferent nerve subtypes most often implicated in cough is provided.
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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.