RELATIONSHIP BETWEEN SMOOTH MUSCLE CONTRACTION AND PHOSPHORYLASE ACTIVATION

¹ Department of Pharmacology, Univerrity of Michigan Medical School, Ann Arbor, Michigan

The effects of various smooth muscle stimulants on the motility and phosphorylase activity of the isolated estrogen-primed rat uterus were studied in an attempt to correlate changes in smooth muscle function with biochemical changes in that tissue. All of the agents tested, including serotonin, acetylcholine, oxytocin, bradykinin and BaCl_2, were found to stimulate both motility and enzyme activity. When the uterine stimulant effect of serotonin was blocked by pretreatment with phenoxybenzamine or methysergide, the phosphorylase activation was also blocked. Similarly, pretreatment with atropine blocked both the uterine stimulation and the phosphorylase activation usually seen after acetylcholine. From these results, it appeared that there was a correlation between the two phenomena. Temporal studies, in which uterine phosphorylase activity was measured at early time intervals after the start of serotonin-induced contractions, indicated that the contraction preceded the phosphorylase activation by at least 4 to 5 sec. Increases in phosphorylase a activity were also observed during spontaneous uterine contractions. When phosphorylase a activity was measured during the peak of a spontaneous contraction, it was greater than during the period of resting tension between contractions. Again, the contraction appeared to precede the phosphorylase activation by 1 to 2 sec. Similar changes in phosphorylase a activity were also observed during spontaneous contractions of guinea pig taenia coli. These results suggest that smooth muscle contraction and phosphorylase activation are related, and that the enzyme activation may be a result of the muscle contraction, since it follows it in time. The mechanism of this activation is unresolved.