Submitted to: Phytomedicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/10/2008
Publication Date: 9/1/2008
Citation: Park, J.B. 2008. Serotomide and safflomide modulate forskolin-stimulated cAMP formation via 5-HT1 receptor. Phytomedicine. http://dx.doi.org/10.1016/j.phymed.2008.04.009.
Interpretive Summary: Interpretive Summary Serotonin (5-HT1) receptors are widely distributed in the central nervous system and other tissues, implicated in physiological processes of psychological and cognitive dysfunction. Due to the physiological importance of such receptors, chemicals that affect them have been explored from natural sources. Interestingly, serotomide and safflomide found in several plants such as Coffea canephora, Theobroma cacao, and Carthamus tinctorius have chemical structures similar to such receptor agents. Therefore, serotomide and safflomide were investigated and found to have effects on the receptors. Currently, compounds which affect the receptors are clinically used for treating several human diseases such as depression, anxiety, migraine, and cognitive dysfunction. Therefore, the outcomes of this study will provide researchers in nutrition, molecular biology, and medicinal fields with new information related to serotomide and safflomide, potent plant-derived bio-active compounds able to affect these serotonin receptors.
Technical Abstract: Serotomide (N-caffeoylserotonin) and safflomide (N-caffeoyltryptamine) are serotonin-derived phenylpropenoid amides found in plants. In this paper, safflomide and serotomide were investigated to determine their effects on serotonin receptor 5-HT1 in the renal epithelial (OK) cells, due to their structural similarity to 5-HT1 receptor ligands. At the concentration of 10 'M, serotomide was able to inhibit forskolin-stimulated cAMP formation in the OK cells by 31% (P < 0.011). The inhibition was repressed by Nan-190 and spiperone (5-HT1 antagonists), suggesting that serotomide suppressed cAMP formation via binding to 5-HT1 receptors in the OK cells. However, safflomide could not inhibit forskolin-stimulated cAMP formation at the same concentration (10 'M), but repressed the inhibition of forskolin-stimulated cAMP by serotonin agonists (e.g., serotonin and 8-OH-DPAT) by 33 % (P < 0.012), suggesting that safflomide may block 5-HT1 receptors in a way similarly to Nan-190 and spiperone. The blocking effect of safflomide was confirmed in OK and Jurkat cells, in which safflomide was able to block [14C]-serotonin binding to the cells expressing 5-HT1 receptors. Altogether, the data indicate that serotomide and safflomide may be potent compounds used as 5-HT1 receptor agonist and antagonist, respectively.