guanylin and Asthma

Asthma is a prevalent respiratory disorder triggered by a variety of inhaled environmental factors, such as allergens, viruses, and pollutants. Asthma is characterized by an elevated activation of the smooth muscle surrounding the airways, as well as a propensity of the airways to narrow excessively in response to a spasmogen (i.e. contractile agonist), a feature called airway hyperresponsiveness. The level of airway smooth muscle (ASM) activation is putatively controlled by mediators released in its vicinity. In asthma, many mediators that affect ASM contractility originate from inflammatory cells that are mobilized into the airways, such as eosinophils. However, mounting evidence indicates that mediators released by remote organs can also influence the level of activation of ASM, as well as its level of responsiveness to spasmogens and relaxant agonists. These remote mediators are transported through circulating blood to act either directly on ASM or indirectly via the nervous system by tuning the level of cholinergic activation of ASM. Indeed, mediators generated from diverse organs, including the adrenals, pancreas, adipose tissue, gonads, heart, intestines, and stomach, affect the contractility of ASM. Together, these results suggest that, apart from a paracrine mode of regulation, ASM is subjected to an endocrine mode of regulation. The results also imply that defects in organs other than the lungs can contribute to asthma symptoms and severity. In this review, I suggest that the endocrine mode of regulation of ASM contractility is overlooked.

Topics: Adaptation, Physiological; Adiponectin; Androgens; Animals; Asthma; Bronchodilator Agents; Dehydroepiandrosterone; Epinephrine; Estrogens; Female; Fibrin; Gastrin-Releasing Peptide; Gastrointestinal Hormones; Glucocorticoids; Humans; Insulin; Leptin; Lung; Male; Muscle Contraction; Muscle, Smooth; Natriuretic Peptides; Progesterone; Respiratory Physiological Phenomena; Respiratory System; Theophylline; Thyroid Hormones; Urokinase-Type Plasminogen Activator

To study the changes of guanylin in asthmatic guinea pig models.. Male guinea pigs were randomly divided into two groups: the control (n = 6) and the asthma group (n = 10). The levels of guanylin in plasma, BALF and lung tissue were measured by RIA kit. The mean thickness of airway wall and glands was determined by contour tracing, using a digitizing pad and microcomputer.. The levels of guanylin in plasma and lung tissue from the asthma group were 56% and 183% higher than those of the control (P < 0.01). Concentrations of guanylin in BALF from the control were below the detection level in 4 guinea pigs, and 1.7 pg/ml and 1.6 pg/ml in two, respectively. The level of guanylin in BALF from asthma group was (3.1 +/- 1.2) pg/ml. The level of guanylin in the lung tissue correlated with that in plasma and BALF (r = 0.72, P < 0.01, r = 0.61, P < 0.05, respectively). The level of guanylin in plasma did not correlate with those of BALF (r = 0.32, P > 0.05). The mean thickness of airway wall and glands in asthma group were 86% and 87% greater than those of the control respectively (P < 0.01). The level of guanylin in lung tissue correlated with the thickness of glands (r = 0.95, P < 0.01).. In the guinea pig model of asthma, guanylin in plasma, BALF and lung tissue were increased, indicating that it may play a role in the mechanism of airway hypersecretion in asthma.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Gastrointestinal Hormones; Guinea Pigs; Lung; Male; Natriuretic Peptides; Peptides; Radioimmunoassay