A historical perspective of pulmonary rapidly adapting receptors

Bronchopulmonary mechanosensors play an important role in the regulation of breathing and airway defense. Regarding the mechanosensory unit, investigators have conventionally adhered to 2 doctrines: one-sensor theory (one afferent fiber connects to a single sensor) and line-labeled theory. Accordingly, lung inflation activates 2 types of mechanosensors: slowly adapting receptors (SARs) and rapidly adapting receptors (RARs) that also respond to lung deflation to produce Hering-Breuer deflation reflex. RARs send signals to a particular brain region to stimulate breathing (labeled as excitatory line) and SARs to a different region to inhibit breathing (inhibitory line). Conventionally, RARs are believed to be mechanosensors, but are also stimulated by a variety of chemicals and mediators. They are activated during different disease conditions and evoke various respiratory responses. In the literature, RARs are the most debatable sensors in the airway. Recent physiological and morphological studies demonstrate that a mechanosensory unit consists of numerous sensors with 4 types, i.e., an afferent fiber connects to multiple homogeneous or heterogeneous sensors (multiple-sensor theory). In addition to SARs and RARs, there are deflation-activated receptors (DARs), which can adapt slowly or rapidly. Each type senses a specific force and generates a unique response. For example, RAR (or SAR) units may respond to deflation if they house DARs responsible for the Hering-Breuer deflation reflex. Multiple-sensor theory requires a conceptual shift because 4 different types of information from numerous sensors carried in an afferent pathway violates conventional theories. Data generated over last eight decades under one-sensor theory require re-interpretation. Mechanosensors and their reflex functions need re-definition. This detailed review of the RARs represents our understanding of RARs under the conventional doctrines, thus it provides a very useful background for interpretation of RAR properties and reflex function against the new proposed multiple-sensor theory.