| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1991: ¥600,000 (Direct Cost: ¥600,000)
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| Research Abstract |
The relationship between contraction changes, cAMP production and beta-adrenergic receptor density under long-term application of ritodrine was investigated using longitudinal muscle strips of pregnant rat uterus. Membrane (-)[^3H] dihydroalprenolol binding sites were increased by 3.1X10^<-8>M ritodrine, with a maximum increase at 3.1X10^<-7>M, followed by a gradual decrease at higher concentrations. Under long-term application of a lower dose (1.5X10^<-7>M) of ritodrine, the number of the binding sites increased up to 20 min, then decreased to the control level and fluctuated after 90 min. In the same condition, cellular cAMP gradually increased up to 20 min, then decreased to the control level and fluctuated after 90 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 1.5X10^<-7>M ritodrine and reactivation after suppression in the presence of the drug. Conseqeuently, the cAMP content of reactivated muscle was significantly lower than that of suppressed muscle, however it was still higher than the control. These results suggest that at lower doses, ritodrine might activate adenylate cyclase, resulting in conformational changes in the receptors, and that receptor dencity might vary in parallel with cellular cAMP production under long-term application of ritrodrine. It is also 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.
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