Purified macrophage mucus secretagogue is a potent bronchial smooth muscle relaxing agent in vitro

Details

• Personal Author:
  Gollub E ; Goswami S ; Maayani S ; Marom Z ; Rienzi N ; Schachter EN ; Zuskin E
• Description:
  We have previously shown that macrophage mucus secretagogue (MMS) a peptide synthesized by alveolar macrophages acts not only as a potent secretagogue of airway mucus but also has the capacity of relaxing airway smooth muscle (ASM) in the guinea pig and in man (ARRD 133:A211,1986). We have recently described a 68Kd protein obtained from human pulmonary macrophages which possesses enhanced secretagogue activity (ARRD 141:A646,1990). We speculate that this molecule may be a precursor for the previously described 2Kd, MMS (J Exper Med 159:844-860, 1984). The smooth muscle relaxing potential of this 68Kd protein (MMS68) was assayed using guinea pig tracheal (GPT) rings suspended in a series of 12 organ baths containing Kreb's Hansielett(sic) (i.e.Krebs-Henseleit) solution at 37 degrees C and pH7.4. Each GPT ring was divided into 4 segments so that each animal served as its own control for the drugs studied, The segments were suspended at 2 grams of baseline tension and relaxation, measured as a percent of this baseline tension. Dose response characteristics were assayed using a stock solution of 1 mg/ml of MMS68 [diluted to 10(-2) mg/ml] delivered in the following concentrations: 5,15,50, 150, 500 ng/ml in the bath. The dose response curve generated had the following response parameters: Emax=55.5 +/- 2.0% (expressed as a percent of the baseline tension = 2 gm) EC50=165 +/- 16 ng, slope = 1.3 +/- 0.1. Contraction of GPT with carbachol [10(-5) M] (C) and histamine [10(-6) M] (H) did not prevent subsequent MMS 68 relaxation of the tissue. Removal of airway epithelium did not alter the response parameters. Pretreatment of the ASM with Indomethacin (I) at a concentrations of 10(-6) M, did not alter MMS68 induced relaxation. We suggest that MMS68 exerts a potent bronchial relaxing effect on both baseline and H and C contracted GPT and that this effect is not mediated by prostaglandin synthesis inhibition. [Description provided by NIOSH]
• Subjects:
  Bicarbonates Biological Assay Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Airway-obstruction Airway-resistance Bioassays Cholinergic-receptors Dose-response Drug-interaction In-vitro-study Laboratory-animals Laboratory-testing Lung-disorders Lung-function Mucous-membranes Muscle-contraction Pharmacodynamics Physiological-effects Protein-biochemistry Proteins Pulmonary-system-disorders Respiratory-system-disorders

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• ISSN:
  0003-0805
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  145
• Issue:
  4
• NIOSHTIC Number:
  nn:20044940
• Citation:
  Am Rev Respir Dis 1992 Apr; 145(4)(Pt 2)(Meeting Abstracts):A374
• CAS Registry Number:
  Carbachol (CAS RN 51-83-2)
• Federal Fiscal Year:
  1992
• NORA Priority Area:
  Pulmonary System Disorders
• Performing Organization:
  Mount Sinai School of Medicine, New York, New York
• Peer Reviewed:
  False
• Part Number:
  2
• Start Date:
  19880701
• Source Full Name:
  American Review of Respiratory Disease
• Supplement:
  Meeting Abstracts
• End Date:
  20020331
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4424184c81e69a87795c0825320ee2234f7808368e4235b3f3f25e05891660b2e24317658279a893ee88a8290edbd7c782abb53953bbca090a590f829c7a7da2
• Download URL:
  https://stacks.cdc.gov/view/cdc/200523/cdc_200523_DS1.pdf
• File Type:
  [PDF - 87.80 KB ]