Ergovaline binding and activation of D2 dopamine receptors in GH4ZR7 cells.
Ergovaline inhibition of radioligand binding to the D2 dopamine receptor and ergot alkaloid inhibition of vasoactive intestinal peptide (VIP)-stimulated cyclic AMP production in GH4ZR7 cells, stably transfected with a rat D2 dopamine receptor, were evaluated. Ergovaline inhibition of the binding of the D2-specific radioligand, [3H]YM-09151-2, exhibited a KI (inhibition constant) of 6.9 +/- 2.6 nM, whereas dopamine was much less potent (370 +/- 160 nM). Ergot alkaloids were also effective in inhibiting VIP-stimulated cyclic AMP production, with EC50 values for ergovaline, ergonovine, alpha-ergocryptine, ergotamine, and dopamine of 8 +/- 2, 47 +/- 2, 28 +/- 2, 2 +/- 1, and 8 +/- 1 nM, respectively. Inhibition of cyclic AMP production by ergovaline was blocked by the dopamine receptor antagonist, (-)-sulpiride (IC50, 300 +/- 150 nM). Our results indicate that ergot compounds, especially ergovaline, bind to D2 dopamine receptors and elicit second messenger responses similar to that of dopamine. These findings suggest that some of the deleterious effects of consumption of endophyte-infected tall fescue, which contains several ergot alkaloids including ergovaline, may be due to D2 dopamine receptor activation.
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Ergot alkaloids cyclic AMP dopamine ergovaline ergonovine alpha-ergocryptine ergotamine dopamine cyclic AMP ergovaline Ergovaline dopamine ergot alkaloid (-)-sulpiride ergovaline dopamine dopamine Ergovaline dopamine vasoactive intestinal peptide D2 dopamine receptor ergot alkaloids VIP rat D2 dopamine receptor D2 VIP D2 dopamine receptor dopamine receptor D2 dopamine receptors D2 dopamine receptors ergovaline dopamine cyclic AMP dopamine Ergovaline [3H]YM-09151-2 dopamine