Stimulatory effect of cinnamic acid analogues on alpha1A-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 C(2)C(12) 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 C(2)C(12) cells. It was shown that methoxylation and/or hydroxylation of cinnamic acid had higher affinities for alpha(1A)-adrenoceptors investigated using [(3)H]prazosin binding experiments in C(2)C(12) cells. The effect of these derivatives on alpha(1A)-adrenoceptors was further characterized using the displacement of [(3)H]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 [(3)H]prazosin binding in rat prostate. Affinity of these compounds for alpha(1B)-adrenoceptors was identified using [(3)H]prazosin-binding experiments in rat spleen. However, we found no marked differences in the IC50 values between these cinnamic acid analogues to displace the [(3)H]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.
Chang
Huang-Kuang
HK
Department of Urology, Mackay Memorial Hospital, Mackay Junior College of Nursing, Taipei City, Taiwan.
Hsu
Feng-Lin
FL
Liu
I-Min
IM
Cheng
Juei-Tang
JT
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D002934:Cinnamates / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
D002934:Cinnamates; D011942:Receptors, Adrenergic, alpha; C029010:cinnamic acid; D005947:Glucose