Pharmacological survey of medicinal plants for activity at dopamine receptor subtypes. II. Screen for binding activity at the D1 and D2 dopamine receptor subtypes

Robert R. Luedtke, Rebekah A. Freeman, Michael Volk, Mohammad Arfan, Manfred G. Reinecke

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Aqueous, organic and alcoholic extracts of 163 Bolivian, Chinese and Pakistani medicinal plants were evaluated for their ability to inhibit the binding of radioligands selective for the D1 and D2 dopamine receptor subtypes expressed in Sf9 cells. Based upon the results of the initial screen, 25 extracts were selected for further evaluation. Concentration-response competitive radioligand binding studies were performed to obtain IC50 values for the inhibition of the binding at D1 or D2 receptors by the selected extracts. The D1 : D2 receptor ratio of IC50 values for the extracts ranged from approximately two-fold selective for the D1 receptor to three-fold selective for the D2 receptor. D1 and D2 dopamine receptors are known to be linked to the activation and inhibition of adenylyl cyclase activity, respectively. Therefore, the selected extracts were tested for the ability to either a) stimulate adenylyl cyclase activity using stably transfected HEK 293 cells expressing human D1 receptors (hD1-HEK) or b) inhibit forskolin-dependent stimulation of adenylyl cyclase activity in stably transfected HEK 293 cells expressing rat D2 dopamine receptors (rD2-HEK). Two extracts were found to stimulate adenylyl cyclase activity in hD1-HEK cells. However, similar results were observed when untransfected HEK cells were used, suggesting that the ability of these two extracts to increase cAMP levels in hD1-HEK cells was not mediated through a D1-like dopamine receptor. While the majority of extracts did not have an effect on forskolin-dependent stimulation in rD2-HEK cells, six extracts were capable of inhibiting adenylyl cyclase activity in these cells. For five of these extracts, the inhibitory effect appeared to be dependent upon the expression of D2 receptors because no inhibitory effect was observed when untransfected HEK 293 cells were used. In summary, the results of this preliminary radioligand binding and functional activity screen of extracts from medicinal plants for pharmacologic activity at D1 and D2 dopamine receptors indicated that the majority of components capable of binding to the D1 and D2 dopamine receptor subtypes appeared to be essentially non-selective. While none of the selected extracts were found to have agonist activity at D1 receptors, several of the extracts exhibited inverse agonist activity at D1 dopamine receptors. Five of the extracts appeared to be agonists at D2 dopamine receptors. Therefore, several classes of extracts were identified which appeared to contained unique combinations of the following pharmacologic properties: D1 dopamine receptor antagonist, D2 dopamine receptor antagonist, D1 receptor inverse agonists and D2 receptor agonists. In addition, two of the extracts tested appeared to modulate adenylyl cyclase activity, but this activity did not appear to be mediated through activation of a dopamine receptor subtype.

Original languageEnglish
Pages (from-to)45-58
Number of pages14
JournalPharmaceutical Biology
Issue number1
StatePublished - Feb 2003


  • Dopamine receptor agonists
  • Dopamine receptor antagonists
  • Dopamine receptors
  • Medicinal plants


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