The effect of selective phosphodiesterase inhibitors on mucociliary activity in the upper and lower airways in vitro.
Bronchodilatory substances such as the phosphodisterase inhibitor (PDE-I) theophylline stimulate mucociliary activity. With the introduction of selective PDE-Is it has become possible to study the functional importance of each phosphodiesterase enzyme (PDE) concerning the regulation of the ciliary beat. The effects of rolipram (inhibiting a cAMP specific PDE (PDE4), milrinone (inhibiting a cGMP inhibited PDE (PDE3)) and zaprinast (inhibiting a cGMP specific PDE (PDE5)) were investigated in in vitro preparations from the rabbit maxillary sinus and trachea. Ciliary beat frequency (CBF) was measured with a photoelectrical method. In sinus mucosa all three compounds accelerated CBF. Milrinone (10(-5) M) by 22.6 +/- 5.3% (n = 6; P < 0.01), rolipram (10(-5) M) by 29.7 +/- 5.7% (n = 7; P < 0.01), and zaprinast (10(-5) M) by 19.4 +/- 6.3% (n = 6; P < 0.05). In the tracheal specimens at a concentration of 10(-5) M, milrinone accelerated CBF by 27.5 +/- 9.0% (n = 7; < 0.05), rolipram by 11.6 +/- 2.8% (n = 6; P < 0.05) and zaprinast by 24.3 +/- 5.3% (n = 7; P < 0.01). Comparison of the effects in the upper and lower airways showed that at concentrations of 10(-5) and 10(-4) M rolipram was more effective in the upper than in the lower airways. The reverse was true of milrinone which concentrations of 10(-7) and 10(-6) M had a significant effect in tracheal specimens but not in sinus specimens. Zaprinast was equally effective in both the upper and lower airways. It is concluded that in both the upper and lower airways selective PDE-Is have an accelerating effect on the CBF that may be beneficial in the treatment of airway diseases.
Cervin
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Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University Hospital, Lund, Sweden. anders.cervin@onh.lu.se
Lindgren
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D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008443:Maxillary Sinus / Q000187:drug effects; D008858:Microscopy, Phase-Contrast; D020105:Milrinone / Q000494:pharmacology; D009079:Mucociliary Clearance / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011688:Purinones / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D012137:Respiratory System / Q000187:drug effects*; D020889:Rolipram; D014132:Trachea / Q000187:drug effects
D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D011760:Pyrrolidinones; C011145:zaprinast; D020105:Milrinone; D020889:Rolipram