Stimulatory effect of cinnamic acid analogues on α1A-adrenoceptors in-vitro

We have characterized the effects of cinnamic acid and its derivatives on alpha(1)-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 alpha(1A)-adrenoceptor subtype of alpha(1)-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 alpha(1A)-adrenoceptors investigated using [H-3]prazosin binding experiments in C2C12 cells. The effect of these derivatives on alpha(1A)-adrenoceptors was further characterized using the displacement of [H-3]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 alpha(1A)-adrenoceptor subtype, showing a smaller IC50 value (the concentration for production of 50% inhibition) to displace [H-3]prazosin binding in rat prostate. Affinity of these compounds for alpha(1B)-adrenoceptors was identified using [H-3]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 alpha(1A)-adrenoceptors.