The effects of the dihydropyridine Bay K 8644 in guinea‐pig isolated trachealis

Open Access
Publisher Website
Google Scholar
Abstract
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 (CaCl2) tested in trachea bathed by a K+-rich, Ca2+-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 Ca2+. 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 Ca2+ influx and its ability to protect against the effects of several structurally-unrelated inhibitors of Ca2+ influx are consistent with Bay K 8644 acting as an agonist at the dihydropyridine receptor associated with the voltage-operated Ca2+ channel (VOC) of trachealis muscle. By this action it potentiates those spasmogens (KCl, TEA) which act by permitting Ca2+ influx through VOCs. In contrast it has no effect on those spasmogens (ACh, histamine) which principally act to liberate Ca2+ from intracellular sites of sequestration.