cholecystokinin and Asthma

Obesity increases asthma prevalence and severity. However, the underlying mechanisms are poorly understood, and consequently, therapeutic options for asthma patients with obesity remain limited. Here we report that cholecystokinin-a metabolic hormone best known for its role in signaling satiation and fat metabolism-is increased in the lungs of obese mice and that pharmacological blockade of cholecystokinin A receptor signaling reduces obesity-associated airway hyperresponsiveness. Activation of cholecystokinin A receptor by the hormone induces contraction of airway smooth muscle cells. In vivo, cholecystokinin level is elevated in the lungs of both genetically and diet-induced obese mice. Importantly, intranasal administration of cholecystokinin A receptor antagonists (proglumide and devazepide) suppresses the airway hyperresponsiveness in the obese mice. Together, our results reveal an unexpected role for cholecystokinin in the lung and support the repurposing of cholecystokinin A receptor antagonists as a potential therapy for asthma patients with obesity.

Topics: Animals; Asthma; Cholecystokinin; Lung; Mice; Mice, Obese; Obesity; Receptor, Cholecystokinin A; Respiratory Hypersensitivity

Topics: Adult; Asthma; Cholecystokinin; Eating; Esophagus; Female; Gastrins; Gastroesophageal Reflux; Gastrointestinal Hormones; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Motilin; Neurotensin; Peristalsis; Somatostatin

To determine the role of gastrointestinal regulatory peptides in exercise-induced asthma (EIA), we studied plasma levels of various gastrointestinal regulatory peptides before and after a 6-min exercise test in seven subjects with EIA and five normal and three asthmatic subjects without EIA. In the EIA group, plasma vasoactive intestinal polypeptide (VIP) rose significantly 5 min and plasma cholecystokinin (CCK) 0 and 20 min after the test compared with the controls. The changes in plasma somatostatin, secretin, pancreatic polypeptide (PP), motilin and insulin showed no significant differences between the two groups. VIP may play an ameliorating role in bronchial asthma, but the relation of CCK to the lung is speculative and awaits further studies.

Topics: Adolescent; Asthma; Asthma, Exercise-Induced; Child; Cholecystokinin; Female; Gastrointestinal Hormones; Humans; Insulin; Male; Motilin; Pancreatic Polypeptide; Physical Exertion; Secretin; Somatostatin; Time Factors; Vasoactive Intestinal Peptide