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The relationship between the drug-receptor interaction and calcium transport in smooth muscle.

The interaction between an agonist and specific receptors in a smooth muscle fiber initiates a series of cellular reactions that lead ultimately to a mechanical response. One of these reactions is the activation of a calcium transport system. Experiments were performed to determine the relationship between the number of receptors occupied by the agonist and the degree of activation of the calcium transport system. The smooth muscles investigated were the longitudinal muscle of the guinea-pig ileum and the thoracic aorta of the rabbit. Acetylcholine was used to stimulate the longitudinal muscle; norepinephrine, the aortic muscle. Dose-response curves were obtained in the presence of a wide range of extracellular calcium ion concentrations. The results were analyzed by a method analogous to that used to determine the dissociation constants of drug-receptor interactions. It was found that the calcium transport system in the longitudinal muscle was activated to near-maximum levels when a small portion of the receptors were filled with acetylcholine. In aortic muscle the relationship was more nearly linear. It would appear, therefore, that the drug-receptor complex does not widen a calcium pore or become a calcium carrier on a one-to-one basis.