title: Increased sensitivity of asthmatic airway smooth muscle cells to prostaglandin E2 might be mediated by increased numbers of E-prostanoid receptors.
abstract: BACKGROUND
  An increase in airway smooth muscle (ASM) cell proliferation leads to an increase in the bulk of the ASM, one of the characteristic features of asthma. We have previously shown that ASM cells from asthmatic individuals proliferate more than those from nonasthmatic subjects. This increased growth might be due to compromised inhibitory mechanisms within the ASM of asthmatic subjects.
  
  
  OBJECTIVE
  The purpose of this study was to determine whether the proliferative control exerted by prostaglandin E(2) (PGE(2)) was altered in the asthmatic ASM cells.
  
  
  METHODS
  We used tritated thymidine uptake to measure cell proliferation and cell-surface ELISAs to detect the presence of cell-surface receptors on ASM cells isolated from asthmatic and nonasthmatic individuals.
  
  
  RESULTS
  The asthmatic ASM cells were significantly more sensitive to proliferation inhibition by PGE(2) than the nonasthmatic cells (P<.02). The PGE(2) (E-prostanoid [EP]) receptors EP2 and EP3 were detected on asthmatic and nonasthmatic smooth muscle cells in culture. There were significantly more receptors on the asthmatic cells. The asthmatic cells also had increased sensitivity to proliferation inhibition by EP2-specific agonists but not by EP3-specific agonists.
  
  
  CONCLUSIONS
  The increased growth observed in asthmatic ASM cells is not the result of impaired responsiveness to PGE(2). In contrast, these cells have increased sensitivity. This increased sensitivity might be mediated by the increased numbers of EP2 receptors on the surface.
authors.affiliation: Respiratory Research Group, Department of Pharmacology, Bosch Building D05, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Janette K
authors.initials: JK
authors.lastname: Burgess
authors.forename: Qi
authors.initials: Q
authors.lastname: Ge
authors.forename: Sarah
authors.initials: S
authors.lastname: Boustany
authors.forename: Judith L
authors.initials: JL
authors.lastname: Black
authors.forename: Peter R A
authors.initials: PR
authors.lastname: Johnson
mesh_terms: D001249:Asthma / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype
chemical_list: C545644:PTGER2 protein, human; C545647:PTGER3 protein, human; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D005576:Colforsin; D011464:Epoprostenol; D015232:Dinoprostone