Effects of calcium channel blockers and a calmodulin antagonist on contractions of guinea pig airways.
Both antigen- and calcium ionophore A23187-induced airways contractions are dependent on increased concentrations of free intracellular calcium. Antigen, but not A23187, contracted airways in the absence of extracellular calcium, suggesting that antigen-induced airways contraction was partly dependent on the mobilization of intracellular calcium. A series of calcium entry blockers and a calmodulin antagonist were examined on airways contraction induced by antigen, A23187, histamine, and LTD4. Verapamil (10(-5)-3 X 10(-4) M) and nitrendipine (3 X 10(-5)-2.8 X 10(-4) M) dose-dependently inhibited antigen-induced contraction of trachea but only partly inhibited antigen-induced contraction of parenchyma and A23187-induced contractions of both trachea and parenchyma. Lanthanum chloride (up to 10(-4) M) and flunarizine (up to 2.1 X 10(-5) M) were relative ineffective. High concentrations of trifluoperazine (1-3 X 10(-4) M) were necessary to inhibit antigen- and A23187-induced airways contractions. Only verapamil and trifluoperazine were effective inhibitors of the responses to histamine and LTD4. In light of the relative ineffectiveness of the above calcium antagonists on the LTD4 dose-response curves, it is suggested that airways contraction is dependent on mobilization of intracellular calcium and that the action of nitrendipine and verapamil as inhibitors of antigen- and A23187-induced contractions is at the point of blocking mediator (i.e. LTC4 and LTD4) release. Verapamil and trifluoperazine also appear to affect contractions. However, the high concentrations of calcium channel and calmodulin antagonists to inhibit antigen- and A23187-induced contractions may limit their usefulness as anti-allergic, anti-asthmatic agents.
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010047:Ovalbumin / Q000494:pharmacology; D013189:SRS-A / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D002121:Calcium Channel Blockers; D002147:Calmodulin; D013189:SRS-A; D000001:Calcimycin; D006632:Histamine; D010047:Ovalbumin; D002118:Calcium