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The effect of L‐type calcium channel modulators on the mobilization of intracellular calcium stores in guinea‐pig intestinal smooth muscle
Author(s) -
Dessy Chantal,
Godfraind Théophile
Publication year - 1996
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.1476-5381.1996.tb15687.x
Subject(s) - ryanodine receptor , diazoxide , chemistry , contraction (grammar) , calcium , nimodipine , histamine , channel blocker , medicine , muscle contraction , endocrinology , calcium channel , voltage dependent calcium channel , dantrolene , biophysics , fura 2 , biology , biochemistry , cytosol , enzyme , organic chemistry , insulin
1 The action of Ca 2+ channel modulators has been examined on the intracellular Ca 2+ signal in the longitudinal smooth muscle cells of the guinea‐pig intestine after exposure to histamine and to agents known to affect intracellular Ca 2+ stores. Isometric contraction has been measured simultaneously with front‐surface fluorometry of fura 2‐loaded preparations. 2 Histamine (10 μ m ) evoked a phasic and tonic increase in [Ca 2+ ] i and contraction which were both sensitive to the Ca 2+ channel blockers, nimodipine and D600. 3 Caffeine (10 mM) evoked in rapid increase in [Ca 2+ ] i which was sustained as long as the preparation was exposed to the drug, whereas the contractile response was only phasic. In the presence of nimodipine 1 μ m , the phasic contraction was absent although the fura 2‐Ca 2+ signal amounted to 32% of the control. 4 Ryanodine (10 μ m ) evoked a slow increase in [Ca 2+ ] i and a contraction, both of which were reversed after exposure to nimodipine (1 μ m ) or D600 (10 μ m ). In the presence of diazoxide (500 μ m ), a hyperpolarizing agent, the ryanodine‐evoked increase in [Ca 2+ ] i and in muscle tone were inhibited. 5 Thapsigargin (1 μ m ) also produced an increase in [Ca 2+ ] i and a contraction both of which were blocked by nimodipine (1 μ m ). 6 In Ca 2+ ‐free solution, histamine 10 μ m evoked non‐reproducible phasic Ca 2+ signal and contraction. This response was recovered after refilling in Ca 2+ containing solution. The recovery was blocked by nimodipine, D600 or diazoxide and was facilitated by the Ca 2+ channel activator, Bay K 8644. When the refilling medium was supplemented with thapsigargin, the recovered response was significantly reduced, but Bay K 8644 still had some action. 7 The present results show that blockade of L‐type Ca 2+ channels inhibited changes in [Ca 2+ ] i evoked by histamine, caffeine and ryanodine which are generally attributed to Ca 2+ mobilization from intracellular stores. They also show that when the tissue was exposed to nimodipine, D600 and diazoxide during the procedure of refilling after depletion of intracellular stores, the action of histamine on [Ca 2+ ] i and contraction was blocked. Bay K 8644 had an opposite effect even when the Ca 2+ pumping activity of the sarcoplasmic reticulum was reduced by thapsigargin. This indicates that refilling of intracellular Ca 2+ stores depleted by histamine in guinea‐pig intestine mainly occurred through L‐type Ca 2+ channels.