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Effects of isoprenaline on the contraction‐relaxation cycle in the cat trachea
Author(s) -
Ito Yushi,
Itoh Takeo
Publication year - 1984
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1984.tb16221.x
Subject(s) - caffeine , isoprenaline , contraction (grammar) , chemistry , acetylcholine , egta , isometric exercise , muscle contraction , tonic (physiology) , calcium , biophysics , endocrinology , medicine , stimulation , biology , organic chemistry
1 Effects of isoprenaline (Isop) on the contractile properties of the smooth muscle cells of cat trachea were investigated using intact and chemically skinned muscle preparations and an isometric tension recording method. 2 In the intact muscle preparations, Isop 3 × 10 −10 or 3 × 10 −9 m significantly suppressed the amplitude of tonic contractions evoked by acetylcholine (ACh) 10 −7 m or 10 −5 m , respectively. 3 Following treatment of the tissue with Ca 2+ ‐free 2 m m EGTA‐containing solution after depletion of stored Ca 2+ with caffeine, 2.5 m m Ca 2+ was applied for 5 min (procedure 1), and subsequently 10 m m caffeine was applied in Ca 2+ ‐free 2 m m EGTA containing solution. The object was to estimate the amount of stored Ca 2+ during procedure 1 from the amplitude of the caffeine (10 m m )‐induced contraction (procedure 2). 4 Isop, applied during procedure 1, did not affect the amplitude of the caffeine‐induced contraction; however, when applied during procedure 2, this agent (10 −8 m ) significantly suppressed the amplitude of the caffeine‐induced contraction to about 90% of the control value. 5 ACh (10 −5 m ), applied during procedure 1, evoked phasic and tonic contractions. Isop (10 −8 m ), applied simultaneously with ACh (10 −5 m ), suppressed the amplitude of the ACh‐induced contraction yet increased the amplitude of contraction evoked by the subsequent application of caffeine 10 m m (procedure 2). 6 Effects of conditioning application of ACh (10 −7 or 10 −5 m ) on the caffeine‐induced contraction were observed in the presence or absence of Isop during procedure 2. When ACh 10 −5 m was used, subsequent application of caffeine 10 m m evoked no mechanical response, in control conditions. However, after the pretreatment of the tissue with Isop during procedure 2, the amplitude of the ACh (10 −5 m )‐induced contraction was not affected, yet the subsequent application of caffeine (10 m m ) evoked minute but discrete contractions, indicating that Isop did enhance the sequestration of free Ca 2+ into the storage sites. 7 In the saponin‐treated skinned muscles, the minimum concentration of Ca 2+ required to produce contraction was 1 × 10 −7 m , and the maximum contraction was obtained with 1 × 10 −5 m Ca 2+ . Isop (10 −6 m ) had no effect on the relationship between free‐Ca 2+ and the amplitude of the contraction. However, simultaneous application of high concentrations of cyclic AMP (10 −4 m ) and cyclic AMP‐dependent protein kinase (50 μg ml −1 ) significantly suppressed contractions evoked by 3 × 10 −7 or 10 −5 m Ca 2+ . 8 These results indicate that Isop suppresses the contraction evoked by various agonists in the cat trachea, mainly through sequestration of Ca 2+ into the intracellular storage sites, rather than by direct or indirect (through cyclic AMP) actions on the contractile proteins.