Mechanical and electrical aspects of the relaxant action of aminophylline in guinea-pig isolated trachealis

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Abstract
1 Aminophylline (1–1000 μmol 1−1) suppressed the spontaneous tone of guinea-pig isolated trachealis in a concentration-dependent manner. 2 In Krebs solution containing acetylcholine (1 mmol 1−1), histamine (200 μmol 1−1) or K+ (120 mmol 1−1) isolated trachealis muscle developed near-maximal tension. The log concentration-effect curve for aminophylline was shifted 20 fold, 3 fold and 4 fold to the right, respectively, in the presence of these spasmogens. 3 Three K+-channel inhibitors were tested: tetraethylammonium (TEA, 8 mmol 1−1) did not modify the action of aminophylline, procaine (5 mmol 1−1) shifted the log concentration-effect curve for aminophylline 2 fold to the left and 4-aminopyridine (5 mmol 1−1) shifted the curve 2.5 fold to the right. 4 Intracellular electrophysiological recording showed that aminophylline 10 μmol 1−1 could cause relaxation in the absence of electrical changes. Higher concentrations of aminophylline (100–1000 μmol 1−1) suppressed spontaneous slow waves and hyperpolarized the trachealis cells. 5 In the presence of procaine (5 mmol 1−1) or TEA (8 mmol 1−1), the hyperpolarization induced by aminophylline (1000 μmol 1−1) was significantly reduced but its relaxant effect was unchanged. 6 In trachealis skinned of its plasma membranes, tension development induced by Ca2+ (20 μmol 1−1) was unaffected either by aminophylline (1000 μmol 1−1) or by isoprenaline (1 μmol 1−1). 7 In studies of the efflux of 86Rb+ from muscle-rich strips of trachea, aminophylline (100–1000 μmol 1−1) was without effect whereas nicorandil (100 and 1000 μmol 1−1) increased the efflux rate constant. 8 It is concluded that aminophylline does not directly reduce the sensitivity of the contractile proteins to cytosolic Ca2+. In low concentration (1–10 μmol 1−1) its relaxant action is not accompanied by membrane potential change but towards the upper end of its effective concentration range, aminophylline evokes hyperpolarization. This hyperpolarization may involve the opening of K+-channels which are inhibited by procaine and (to a lesser extent) by TEA. These K+-channels may be impermeable to 86Rb+.

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