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Smooth muscle tissues were contracted by excitation of each muscle cell. Single cells prepared from guinea pig taenia caecum and trachea were contracted by extracellular application of acetylcholine and/or carbachol, whose concentrations were the same as those in the tissues. The concentration-response curve was shifted in a parallel fashion by competitive antagonists. The pA2-values of the antagonists were in good agreement with those estimated using the intact tissue. The apparent dissociation constants of cholinergic drugs estimated from inhibition of the specific binding of [3H]QNB (quinuclidinyl benzilate) to the single cells by the cholinergic drugs were also in agreement with the values in other membrane preparations. Similar findings were obtained in the single cells, microsomal fractions and isolated tissues from the guinea pig tracheal smooth muscles. In rabbit aortic single cells, the existence of two pharmacologically distinct alpha 1-adrenoceptor subtypes, alpha 1A and alpha 1B, in vascular smooth muscle cells was supported. Furthermore, the amount of prostaglandin F2 alpha released from guinea pig tracheal single cells was increased through activation by alpha 2-adrenoceptor agonists. The amount of prostaglandin F2 alpha released by norepinephrine decreased with age, while the total amount of alpha 2-adrenoceptors and the dissociation constants of the alpha 2-adrenergic drugs from the receptor did not change. The relaxation induced by beta-adrenoceptors did not alter with age. The total amount of beta-adrenoceptor and the dissociation constants of beta-adrenergic drugs from their receptor did not alter with age. An excellent relationship between the potency of isoprenaline and the maximum binding of [3H]dihydroalprenolol estimated in the single cells from 6- to 40-week-old guinea pigs was found, suggesting that the increase in the potency of isoprenaline is due to the increase in the maximum binding. The value in the single cells from 100-week-old guinea pigs deviated significantly from the regression line. This result suggests that the decrease in potency in the single cells from 100-week-old animals is due to a change in post beta-receptor processes in responsiveness. The smooth muscle single cells are useful for the study of drug-receptor interactions. Furthermore, post-receptor processes in responsiveness were discussed.

Pharmacological Studies in Isolated Smooth Muscle Cells. Drug-receptor interactions in single smooth muscle cells.