We have characterized the effects of cinnamic acid and its derivatives on α1A-adrenoceptor subtypes. The cinnamic acid with a methoxyl group and/or a hydroxyl group showed the ability to stimulate radioactive glucose uptake into C2C12 cells, a cell line that specifically expresses the α1A-adrenoceptor subtype of α1-adrenoceptors. However, cinnamic acid without chemical modification diminished the glucose uptake into C2C12 cells. It was shown that methoxylation and/or hydroxylation of cinnamic acid had higher affinities for α1A-adrenoceptors investigated using [3H]prazosin binding experiments in C2C12 cells. The effect of these derivatives on α1A-adrenoceptors was further characterized using the displacement of [3H]prazosin binding in rat prostate. We found that 3,5-dimethoxy-4-hydroxycinnamic acid, the cinnamic acid derivative with two methoxyl groups and hydroxylation at the fourth carbon on the benzene ring, had a higher affinity for the α1A-adrenoceptor subtype, showing a smaller IC50 value (the concentration for production of 50% inhibition) to displace [3H]prazosin-binding in rat prostate. Affinity of these compounds for α1B-adrenoceptors was identified using [3H]prazosin-binding experiments in rat spleen. However, we found no marked differences in the IC50 values between these cinnamic acid analogues to displace the [3H]prazosin binding in rat spleen. In conclusion, our data indicated that methoxylation and/or hydroxylation of cinnamic acid might raise the affinity for α1A-adrenoceptors.
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