Expression of urocortin in rat lung and its effect on pulmonary vascular permeability.
Urocortin (UCN), a newly identified, 40-amino-acid, corticotropin-releasing hormone (CRH) structurally related peptide, has been demonstrated to be expressed in the central nervous system and many peripheral tissues of rats and man. This study aimed to investigate the expression profile of UCN in rat lung and the effect of UCN on lung vascular permeability. The expression of UCN mRNA was detected by reverse transcriptase PCR (RT-PCR). UCN peptide was measured by immunohistochemistry and Western blot analysis. We found that both UCN mRNA and peptide were obviously expressed in rat lung. Immunohistochemistry results showed that UCN peptide is mainly expressed in bronchial epithelium mucosa and alveolar epithelium. We also found that rats receiving inhalation aerosol of UCN had a significant elevation of lung vascular permeability compared with rats receiving vehicle and ovalbumin (OVA) by the Evans blue (EB) technique. UCN aerosol inhalation resulted in obvious pulmonary congestion and edema observed under light microscope by hematoxylin and eosin (HE) staining. The nonselective peptide CRH receptor antagonist astressin markedly reduced lung vascular permeability triggered by UCN. Enhanced pulmonary vascular permeability induced by UCN was markedly inhibited by pretreatment with the mast-cell stabilizer cromolyn and histamine-1 (H1) receptor antagonist azelastine respectively, but not by the leukotriene receptor antagonist montelukast. In summary, in the present study, we demonstrated for the first time that UCN is expressed in rat lung and contributes to an increase in lung vascular permeability through activation of CRH receptors. Mast cells and histamine may be involved in this effect of UCN. Peripherally produced UCN in lung may act as an autocrine and paracrine proinflammatory factor.
Wu
Yuqing
Y
Department of Pharmacology, Nanjing Medical University, Nanjing, 210029, P R China.
Xu
Yinyan
Y
Zhou
Hong
H
Tao
Jin
J
Li
Shengnan
S
D000085:Acetates / Q000494:pharmacology; D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001980:Bronchi / Q000737:chemistry / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D003521:Cyclopropanes; D004848:Epithelium / Q000737:chemistry / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D020024:Leukotriene Antagonists / Q000494:pharmacology; D008168:Lung / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D010047:Ovalbumin / Q000008:administration & dosage; D010446:Peptide Fragments / Q000494:pharmacology; D010793:Phthalazines / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000737:chemistry / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013440:Sulfides; D054832:Urocortins
D000085:Acetates; D000336:Aerosols; D003521:Cyclopropanes; D006634:Histamine H1 Antagonists; D020024:Leukotriene Antagonists; D010446:Peptide Fragments; D010793:Phthalazines; D011804:Quinolines; D012333:RNA, Messenger; D013440:Sulfides; D054832:Urocortins; C104416:astressin; D010047:Ovalbumin; D003346:Corticotropin-Releasing Hormone; C093875:montelukast; D004205:Cromolyn Sodium; C020976:azelastine