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Inositol 1,4,5‐trisphosphate‐ and guanosine 5′‐O‐(3‐thio triphosphate)‐induced Ca 2+ release in cultured airway smooth muscle
Author(s) -
Chopra Lorna C.,
Twort Charles H.C.,
Cameron Ian R.,
Ward Jeremy P.T.
Publication year - 1991
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.1476-5381.1991.tb12524.x
Subject(s) - gtp' , ryanodine receptor , inositol , guanosine , calcium , inositol trisphosphate , egta , chemistry , caffeine , biophysics , intracellular , biochemistry , medicine , endocrinology , biology , enzyme , receptor , organic chemistry
1 The interaction between inositol 1,4,5‐trisphosphate (InsP 3 ) and guanosine 5′‐O‐(3‐thio triphosphate) (GTPγS) releasable calcium (Ca 2+ ) pools was examined using 45 Ca effluxes in permeabilized cultured airway smooth muscle cells from rabbit trachea. 2 Addition of InsP 3 or GTPγS caused a concentration‐dependent release of intracellular Ca 2+ . The release of Ca 2+ by InsP 3 was much greater than with GTPγS. Pretreatment with maximally effective InsP 3 (10 μ m ) abolished the GTPγS‐induced Ca 2+ release, whereas pretreatment with 100 μ m GTPγS reduced the InsP 3 ‐induced Ca 2+ release by 25%. 3 Ryanodine (100 μ m ), also gave a large release of intracellular Ca 2+ . After pretreatment with 100 μ m ryanodine, GTPγS did not induce Ca 2+ release, and InsP 3 ‐induced Ca 2+ release was reduced by 76%. 4 Caffeine (50 m m ), produced a slow release of intracellular Ca 2+ . Pre‐exposure to 50 m m caffeine had no effect on the GTPγS‐induced Ca 2+ release but reduced the InsP 3 releasable Ca 2+ by 58%. 5 Pretreatment with ryanodine abolished the caffeine‐induced Ca 2+ release, and addition of caffeine before ryanodine reduced the ryanodine‐induced Ca 2+ release by 64.4%. 6 These results suggest that there are at least three pools of Ca 2+ present within airway smooth muscle cells. The largest pool is released by InsP 3 or ryanodine, another is released either by a high concentration of InsP 3 or on application of GTPγS, and the third by InsP 3 alone. Ca 2+ may be able to move from the GTPγS‐sensitive pool into the InsP 3 ‐ and ryanodine‐sensitive pool when this becomes depleted. In contrast, the opposite movement of Ca 2+ cannot occur.