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Mechanism of carbachol‐evoked contractions of guinea‐pig ileal smooth muscle close to freezing point
Author(s) -
Blackwood A.M.,
Bolton T.B.
Publication year - 1993
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.1476-5381.1993.tb13725.x
Subject(s) - carbachol , calcium , contraction (grammar) , chemistry , muscle contraction , biophysics , medicine , endocrinology , depolarization , potassium , stimulation , biology , organic chemistry
1 The effect of lowering the temperature to near freezing‐point upon the contractions and [ 3 H]‐inositol phosphate responses to carbachol were investigated in longitudinal smooth muscle from the guinea‐pig ileum. 2 The peak amplitude of the contraction to a single application of 100 μ m carbachol was the same at 37°C and temperatures near freezing‐point. However, the sensitivity to carbachol was reduced upon lowering the temperature and the time to peak contraction was increased from 5–10 s to 2–10 min. Even when the temperature was maintained near freezing‐point, washing off carbachol produced a relaxation and eventual return of tension to basal levels. 3 Incubating the tissue in 140 m m K + , calcium‐free solution or in calcium channel antagonists significantly reduced the carbachol‐induced contraction to 10–30% of the control at 37°C and also at 3°C. Thus the majority of the activator calcium required for contraction entered the tissue via voltage‐dependent calcium channels (VDCs) at both 37°C and 3°C. 4 The contractions produced by high potassium solutions were less at temperatures close to freezing‐point than those at 37°C suggesting that voltage‐dependent calcium entry was inhibited as the temperature was lowered. 5 A small part of the contractile response to 100 μ m carbachol was resistant to the removal of extracellular calcium at both 37°C and 3°C and this component was increased under depolarizing conditions. This suggests that the release of stored calcium contributes to a minor degree to contraction at both 37°C and 3°C. 6 Although 100 μ m carbachol produced a statistically significant rise in several [ 3 H]‐inositol phosphate isomers at both 37°C and 3°C, the production of [ 3 H]‐inositol phosphates was less at 3°C than at 37°C and the increase in their production caused by carbachol was much slower. 7 These results suggest that the carbachol‐induced contraction at 3°C utilizes both calcium entry through VDCs and calcium release from intracellular stores, as at 37°C. The components of the responses dependent upon intracellular calcium release at 37°C and at temperatures near freezing‐point were similar. However, the production of [ 3 H]‐inositol phosphates, including the calcium‐mobilizing second messenger inositol (1,4,5) trisphosphate (Ins(1,4,5)P 3 ), is reduced at such low temperatures.