Gamma-aminobutyric acid: something old, something new for bronchodilation.

摘要

EXAGGERATED airway narrowing but impaired relaxation in diseases such as asthma is mediated by altered airway smooth muscle (ASM) response to bronchoconstrictors and bronchodilators. The considerable progress in understanding cellular mechanisms that regulate ASM contractility and hyperresponsiveness is underlined by established clinical use of beta-adrenoceptor agonists, leukotriene inhibitors, and steroids. On the other hand, increasing asthma prevalence, especially in children, and advertisements for "me-too" asthma therapies targeting the same, established cellular mechanisms underscores the need for new phar-macologic treatment approaches. Although anesthesiologists have long used the bronchodilatory properties of some inhalational agents (e.g., sevoflurane) and intravenous anesthetics (e.g., propofol) to resolve intraoperative bron-chospasm, this approach is impractical outside the operating room. In this issue of Anesthesiology, Gallos et al. have unVeiled a new (and yet not that new!) potentialtarget to produce bronchodilation: gamma-aminobutryic acid (GABA) signaling in the airway. But it is not the known role of GABA and GABA receptors in brainstem and preganglionic cho-linergic innervation to the airway that they discuss. Using an in vitro guinea pig airway model, they demonstrate endogenous GABA release (enhanced by agonist stimulation) that can induce bronchodilation. Furthermore, using the positive allosteric properties of propofol, they show that propofol-induced bronchodilation may be partly attributable to GABA. This paper is the latest in a series of reports by this group highlighting the role of functional GABA receptors in the airway. Although still in the investigational phase, these studies provide hope for a new approach to both outpatient and perioperative interventions to treat acute bronchoconstriction.