Purified macrophage mucus secretagogue is a potient bronchial smooth muscle relaxing agent in vitro.
Schachter-EN; Zuskin-E; Marom-Z; Goswami-S; Gollub-E; Rienzi-N; Maayani-S
Am Rev Respir Dis 1992 Apr; 145(4)(Pt 2)(Meeting Abstracts):A374
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.
Respiratory-system-disorders; Pulmonary-system-disorders; Lung-disorders; Lung-function; Airway-obstruction; Airway-resistance; Laboratory-animals; Laboratory-testing; Mucous-membranes; Muscle-contraction; Dose-response; In-vitro-study; Protein-biochemistry; Proteins; Bioassays; Drug-interaction; Pharmacodynamics; Cholinergic-receptors; Bicarbonates; Physiological-effects
American Review of Respiratory Disease
Mount Sinai School of Medicine, New York, New York