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The effects of the dihydropyridine Bay K 8644 in guinea‐pig isolated trachealis
Author(s) -
Allen S.L.,
Foster R.W.,
Small R.C.,
Towart R.
Publication year - 1985
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.1476-5381.1985.tb09447.x
Subject(s) - nifedipine , chemistry , tetraethylammonium chloride , trachealis muscle , verapamil , calcium , histamine , tetraethylammonium , endocrinology , acetylcholine , medicine , dihydropyridine , potassium , biology , organic chemistry , charybdotoxin
1 In trachea bathed by Krebs solution containing indomethacin 0.8 μmol 1 −1 , Bay K 8644 (0.01‐1 μmol 1 −1 ) evoked mild spasm. Peak tension was achieved after 10 min and was generally less than 20% of an acetylcholine (ACh) maximum. The effect of Bay K 8644 was not potentiated by addition of 2.5 mmol 1 −1 potassium chloride (KCl) to the Krebs solution. 2 Bay K 8644 (1 μmol 1 −1 ) caused a small potentiation of KCl and tetraethylammonium (TEA). In contrast it did not modify the actions of ACh or histamine. 3 Bay K 8644 (1 μmol 1 −1 ) caused a small potentiation of the effect of calcium chloride (CaCl 2 ) tested in trachea bathed by a K + ‐rich, Ca 2+ ‐free, MOPS‐buffered physiological salt solution. 4 Organic inhibitors of calcium influx such as nifedipine (0.1 μmol 1 −1 ), verapamil (1 μmol 1 −1 ) or diltiazem (10 μmol 1 −1 ) each caused marked depression of concentration‐effect curves to KCl. Bay K 8644 (0.01‐1 μmol 1 −1 ) provided concentration‐dependent protection against this effect in all three cases. 5 Estimation of calcium influx by the lanthanum technique revealed that Bay K 8644 (1 μmol 1 −1 ) was able to promote the cellular influx of Ca 2+ . 6 Intracellular electrophysiological recording showed that Bay K8644 (1 μmol 1 −1 ) caused no change in the resting membrane potential of trachealis cells and no change in the properties of the spontaneous electrical slow waves. However, Bay K 8644 was able to delay the slow wave suppression evoked by 1 μmol 1 −1 nifedipine. 7 The ability of Bay K 8644 to promote Ca 2+ influx and its ability to protect against the effects of several structurally‐unrelated inhibitors of Ca 2+ influx are consistent with Bay K 8644 acting as an agonist at the dihydropyridine receptor associated with the voltage‐operated Ca 2+ channel (VOC) of trachealis muscle. By this action it potentiates those spasmogens (KCl, TEA) which act by permitting Ca 2+ influx through VOCs. In contrast it has no effect on those spasmogens (ACh, histamine) which principally act to liberate Ca 2+ from intracellular sites of sequestration.