Endogenous opioids as mediators of asthma.
Changes in airway innervation are believed to play a key role in the pathophysiology of asthma. A group of regulatory peptides which act as neuroregulators is resembled by the opioids. Their localization to neurons projecting into airways suggested a possible role as regulators of neurogenic inflammation, bronchoconstriction and mucus secretion. They mainly act through modification of tachykinergic and cholinergic impulses and their ability to inhibit bronchoconstriction prompted discussion of their potential value in asthma therapy. Apart from the presence of the classical opioids and their receptors in the lung and their functional role, a new group of peptides such as nociceptin and endomorphins have been characterized in the airways. Whereas at least endomorphin-1 acts via the classical OP(3) (mu) receptor, nociceptin binds to a new receptor termed opioid receptor-like-receptor (ORL(1)) and inhibits tachykinergic constriction. Contrary to these promising modulatory effects on airway smooth muscle tone, effective therapeutic strategies have not been developed yet. In conclusion, opioids resemble a group of regulatory peptides which are present within airway-innervating nerve fibres and influence a multitude of airway functions via modification of neural transmission.
Groneberg
D A
DA
Division of Allergy Research, Department of Pediatric Pneumology and Immunology, Humboldt-University, Berlin, Germany. david.groneberg@charite.de
Fischer
A
A
D001249:Asthma / Q000503:physiopathology*; D016084:Bronchoconstriction; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000294:innervation*; D009474:Neurons / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000502:physiology*; D015398:Signal Transduction; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C105293:endomorphin 1; C000722283:OPRL1 protein, human