Effects of Bay K 8644 on contraction of the human isolated bronchus and guinea‐pig isolated trachea

Abstract

1 The effects of Bay K 8644, a dihydropyridine which increases calcium flux through the potential-operated channels were studied on the contractions induced by histamine, acetylcholine, KCl and Ca²⁺ on human isolated bronchial strips and the results were compared to those obtained on guinea-pig isolated tracheal spirals. Subsequently the contractant effects of Bay K 8644 in K⁺-enriched medium and in the presence of Ca²⁺ 0.03 mM were investigated. 2 In Krebs normal calcium medium, Bay K 8644 did not significantly modify the EC₅₀ of acetylcholine or histamine on the human bronchus, but in concentrations of 10⁻⁷ − 10⁻⁶ M it potentiated the effects of KCl on that preparation. It did not modify the EC₅₀ of acetylcholine, histamine or KCl on the guinea-pig trachea. 3 In Ca²⁺-free Krebs medium with additional K ⁺ (30 mM), Ca²⁺ concentration-response curves were displaced to the left by Bay K 8644 in the two preparations. Shifts were 0.52 ± 0.11 and 0.72 ±0.16 log units respectively with Bay K 8644 10⁻⁸ and 10⁻⁷ M on human bronchus (n = 4) and 0.67 ± 0.16 and 1.06 ± 0.19 log units respectively with Bay K 8644 10⁻⁷ and 10⁻⁶ M on the guinea-pig trachea (n = 5). 4 In Krebs medium with Ca²⁺ 0.03 mM and K⁺ 30 mM, Bay K 8644 (10⁻⁸ to 10⁻⁶ M) contracted both the human bronchus and the guinea-pig isolated trachea. This effect was competitively antagonized by nicardipine. 5 These results demonstrate the presence of dihydropyridine sites of action on human bronchus and confirm the minor role played by Ca²⁺ influx through potential-operated channels in the contractile effects of acetylcholine or histamine. They also demonstrate the similar reactivity of human bronchus and guinea-pig isolated trachea to Bay K 8644.