Novel concepts of neuropeptide-based drug therapy: vasoactive intestinal polypeptide and its receptors.
Chronic inflammatory airway diseases such as bronchial asthma or chronic obstructive pulmonary disease (COPD) are major contributors to the global burden of disease. Although inflammatory cells play the central role in the pathogenesis of the diseases, recent observations indicate that also resident respiratory cells represent important targets for pulmonary drug development. Especially targeting airway neuromediators offers a possible mechanism by which respiratory diseases may be treated in the future. Among numerous peptide mediators such as tachykinins, calcitonin gene-related peptide, neurotrophins or opioids, vasoactive intestinal polypeptide (VIP) is one of the most abundant molecules found in the respiratory tract. In human airways, it influences many respiratory functions via the receptors VPAC1, VPAC2 and PAC1. VIP-expressing nerve fibers are present in the tracheobronchial smooth muscle layer, submucosal glands and in the walls of pulmonary and bronchial arteries and veins. Next to its strong bronchodilator effects, VIP potently relaxes pulmonary vessels, and plays a pivotal role in the mediation of immune mechanisms. A therapy utilizing the respiratory effects of VIP would offer potential benefits in the treatment of obstructive and inflammatory diseases and long acting VIP-based synthetic non-peptide compounds may represent a novel target for drug development.
Groneberg
David A
DA
Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany. groneberg.david@mh-hannover.de
Rabe
Klaus F
KF
Fischer
Axel
A
D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D001993:Bronchodilator Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D009093:Mucus / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism; D011487:Protein Conformation; D016032:Randomized Controlled Trials as Topic; D018005:Receptors, Vasoactive Intestinal Peptide / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014630:Vagus Nerve / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D014664:Vasodilation
D001993:Bronchodilator Agents; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide