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Influence of cartilage on reactivity and on the effectiveness of verapamil in guinea pig isolated airway smooth muscle.

Raeburn-D; Hay-DW; Farmer-SG; Fedan-JS
J Pharmacol Exp Ther 1987; 242(2):450-454
The effect of cartilage removal on the response of guinea-pig trachealis to bronchoconstrictors and the antispasmogenic and spasmolytic agent verapamil was studied. Basal calcium uptake by guinea-pig trachealis was known to be reduced by cartilage removal. Trachealis isolated from male English-short-hair-guinea-pigs showed decreased sensitivity to potassium-chloride and histamine in the absence of cartilage, consistent with the reported extracellular calcium dependency of these agents. In contrast, a change in sensitivity to methacholine was seen, consistent with the suggestion that this agent acts via intracellular calcium pools. High potassium-chloride concentrations showed a lesser effect of cartilage removal, suggesting that intracellular calcium might be utilized in its stimulation of smooth muscle contraction. Cartilage removal increased the antispasmogenic and spasmolytic effects of verapamil on contraction induced by histamine and methacholine. Verapamil was more effective at blocking existing contractions than preventing their development. This was consistent with the proposal that verapamil blocks the smaller influx of calcium occurring during the sustained secondary phase of contraction. A "use dependence" for verapamil was seen, which was similar to the effect seen in cardiac muscle. Possible mechanisms for this effect were discussed. The authors conclude that removal of cartilage reduces muscle reactivity and increases the potency of verapamil in guinea-pig trachealis, suggesting a role for cartilage derived calcium in excitation/contraction coupling mechanisms.
NIOSH-Author; In-vitro-studies; Muscle-tissue; Pharmacology; Laboratory-animals; Pulmonary-system; Muscle-contraction; Drugs
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Journal of Pharmacology and Experimental Therapeutics