ERGOVALINE BINDING AND ACTIVATION OF D2 DOPAMINE-RECEPTORS IN GH(4)ZR(7) CELLS

Ergovaline inhibition of radioligand binding to the D-2 dopamine recep tor and ergot alkaloid inhibition of vasoactive intestinal peptide (VI P)-stimulated cyclic AMP production in GH(4)ZR(7) cells, stably transf ected with a rat D-2 dopamine receptor, were evaluated. Ergovaline inh ibition of the binding of the D-2-specific radioligand, [H-3]YM-09151- 2, exhibited a K-I (inhibition constant) of 6.9 +/- 2.6 nM, whereas do pamine was much less potent (370 +/- 160 nM). Ergot alkaloids were als o effective in inhibiting VIP-stimulated cyclic AMP production, with E C(50) values for ergovaline, ergonovine, alpha-ergocryptine, ergotamin e, and dopamine of 8 +/- 2, 47 +/- 2, 28 +/- 2, 2 +/- 1, and 8 +/- 1 n M, 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 er govaline, bind to D-2 dopamine receptors and elicit second messenger r esponses 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, m ay be due to D-2 dopamine receptor activation.