The significance of adenosine cyclic 3',5'-monophosphate for the contraction of smooth muscle.

1. The influence of adenosine cyclic 3',5'-monophosphate (3',5'-AMP) and of drugs believed to increase or decrease its concentration in the tissues has been determined on the response of vascular and uterine smooth muscles to catecholamines. Generally, drugs believed to increase tissue content of 3',5'-AMP potentiated the responses and those believed to decrease it depressed them.2. The cardiovascular responses of dogs (with major vessels occluded in the chest) to carotid occlusion were potentiated by infusions of theophylline and sodium fluoride. Infusion of theophylline also potentiated the response of the occluded abdominal vessels to noradrenaline.3. Intravenous infusions of theophylline and sodium fluoride potentiated pressor responses to catecholamines in the pithed rat. Infusions of iminazole depressed the responses in two animals and was without effect in two others.4. In spinal cats intravenous infusions of theophylline potentiated pressor responses to catecholamines, but sodium fluoride was without effect.5. Contractions of the isolated rat aortic strip to noradrenaline were always potentiated by sodium fluoride and by theophylline, and depressed by iminazole, when they were recorded isometrically. Theophylline always potentiated the contractions, when they were recorded isotonically but sodium fluoride was mostly, and iminazole always, ineffective.6. 3',5'-AMP in concentrations from 0.1 to 20 mug/ml. potentiated the responses of the isolated rat aortic strip to noradrenaline in thirty-eight experiments out of hundred. Concentrations from 10 to 500 mug/ml. sometimes depressed contractions recorded isometrically. In five experiments, exposure to low concentrations for 3 hr increased the resting tension of the preparation.7. Responses to noradrenaline of uteri from oestradiol-treated rabbits were potentiated by vasopressin and by sodium fluoride, but not by theophylline or iminazole. In progesterone-treated animals the responses were unaffected by vasopressin and sodium fluoride, but potentiated by theophylline and depressed by iminazole. 3',5'-AMP was without effect on the uterine responses.8. It is concluded that the results support the view that an increase in the tissue content of 3',5'-AMP potentiates the contraction of vascular and uterine smooth muscle in response to catecholamine. This view is supported by the observation that the nucleotide itself can potentiate the responses of the rat aortic strip to noradrenaline.