Dopamine and Serotonin Modulate Human GABAρ1 Receptors Expressed in Xenopus laevis Oocytes

GABA rho 1 receptors are highly expressed in bipolar neurons of the retina and to a lesser extent in several areas of the central nervous system (CNS), and dopamine and serotonin are also involved in the modulation of retinal neural transmission. Whether these biogenic amines have a direct effect on ionotropic GABA receptors was not known. Here, we report that GABA rho 1 receptors, expressed in X. laevis oocytes, were negatively modulated by dopamine and serotonin and less so by octopamine and tyramine. Interestingly, these molecules did not have effects on GABA(A) receptors. S-Carboxamido-tryptamine and apomorphine did not exert evident effects on any of the receptors. Schild plot analyses of the inhibitory actions of dopamine and serotonin on currents elicited by GABA showed slopes of 2.7 +/- 0.3 and 6.1 +/- 1.8, respectively, indicating a noncompetitive mechanism of inhibition. The inhibition of GABA rho 1 currents was independent of the membrane potential and was insensitive to picrotoxin, a GABA receptor channel blocker and to the GABA rho-specific antagonist (1,2,5,6-tetrahydropyridine-4-yl)methyl phosphinic acid (TPMPA). Dopamine and serotonin changed the sensitivity of GABA rho 1 receptors to the inhibitory actions of Zn2+. In contrast, La3+ potentiated the amplitude of the GABA currents generated during negative modulation by dopamine (EC50 146 mu M) and serotonin (EC50 196 mu M). The functional role of the direct modulation of GABA rho receptors by dopamine and serotonin remains to be elucidated; however, it may represent an important modulatory pathway in the retina, where GABA rho receptors are highly expressed and where these biogenic amines are abundant.