Relationship between changes in contraction and cyclic AMP contents under long-term application of ritodrine in...

The relationship between contraction changes and cAMP production under long-term application of ritodrine was investigated using longitudinal muscle strips of pregnant (Day 21) rat uterus. Cellular cAMP gradually increased up to 20 min, then decreased to the control level and fluctuated after 90 min in the presence of 1.5 x 10(-7) M ritodrine. When the dose was raised to 3.1 x 10(-4) M, cAMP contents markedly increased. However, it then decreased after 30 min and reached the control level after 180 min. To clarify the actual relationship between the changes in spontaneous contraction and cAMP contents of the same muscle strips, the strips were obtained during control contraction, suppression by 1.5 x 10(-7) M ritodrine and reactivation after suppression in the presence of the drug. Consequently, the cAMP content of reactivated muscle was significantly lower than that of suppressed muscle (p less than 0.01), however it was still higher than the control (p less than 0.05). It is speculated that the reactivation of spontaneous contractions might not depend solely on the cellular cAMP level, and that another activating mechanism, such as changes in ion permeability, might be involved in this type of desensitization phenomenon.