Guanine nucleotides reveal differential actions of ergot derivatives at D-2 receptors labelled by ( super(3)H)spiperone in striatal homogenates

The specific binding of ( super(3)H)spiperone (35 pM), as defined by the D-2 antagonist sulpiride, was potently displaced by ergot derivatives of both the ergoline and ergopeptine type, and by dopamine agonists and antagonists. The potency of the ergot derivatives ranged widely from an IC sub(50) value of 3 nM for bromocriptine to a value of 1000 nM for the partial ergoline, LY-141865. GTP and its stable analogue, guanyl-5'-yl-imidodiphosphate (Gpp(NH)p), did not affect the affinity (100 pM) or density (30 pmol/g wet wt) of ( super(3)H)spiperone binding sites, but did decrease the potency of a number of ergoline compounds including pergolide, lergotrile and LY-141865, as well as dopamine agonists to displace ( super(3)H)spiperone binding. The affinities of the ergopeptines, bromocriptine and dihydroergocryptine, and of the isolsergic acid ergoline, lisuride, and dopamine antagonists were unaltered by the presence of guanine nucleotides.