title: Local pulmonary opioid network in patients with lung cancer: a putative modulator of respiratory function.
abstract: Recently, there has been growing interest in the opioid regulation of physiological respiratory function. However, evidence for a local opioid network that includes endogenous opioid peptides and their receptors is scarce. Tissue samples from patients with lung cancer were examined by immunohistochemistry to identify the components of the opioid network: beta-endorphin (END); its precursor, proopiomelanocortin (POMC); the key processing enzymes prohormone convertase 1 and 2; carboxypeptidase E; and END's corresponding opioid receptor, the mu-opioid receptor (MOR). Additionally, we tested pulmonary function parameters in a patient with advanced lung cancer after inhalation of nebulized morphine. Confocal immunofluorescence microscopy revealed that the opioid precursor POMC colocalizes with its active peptide END, key processing enzymes and MOR in alveolar macrophages, submucosal glands, cancerous cells, and pulmonary neuroendocrine cells within the bronchial epithelium. In addition, MOR was identified on sensory nerve endings within the bronchial epithelium. Furthermore, nebulized morphine improved pulmonary function parameters in advanced lung cancer. These findings provide evidence of a local opioid network in functionally important anatomical structures of the respiratory system; this network consists of all the machinery required for POMC processing into active peptides, such as END, and contains the receptors for END. Our findings indicate a need for further clinical trials to elucidate the modulatory function of peripheral endogenous opioids in the human lung.
authors.affiliation: Palliative Care Department, Collegium Medicum of the Nicolaus Copernicus University, Skłodowskiej-Curie 9, PL 85-094 Bydgoszcz, Poland. malgorzata.krajnik@wp.pl
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krajnik
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfer
authors.forename: Piotr
authors.initials: P
authors.lastname: Sobański
authors.forename: Janusz
authors.initials: J
authors.lastname: Kowalewski
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Bloch-Bogusławska
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Zylicz
authors.forename: Shaaban A
authors.initials: SA
authors.lastname: Mousa
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D004723:Endorphins / Q000502:physiology*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000503:physiopathology*; D008175:Lung Neoplasms / Q000503:physiopathology*; D008297:Male; D018613:Microscopy, Confocal; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000502:physiology; D012129:Respiratory Function Tests; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D004723:Endorphins; D017450:Receptors, Opioid, mu; D011333:Pro-Opiomelanocortin; D009020:Morphine