After cerebral cortical membranes were incubated with 0.1-100 μM of dopamine (DA) in 50 mM Tris-HCl buffer (pH 7.7) at 37°C for 30 min, [
3H] clonidine binding to α
2-receptors was increased in a concentration-dependent manner without changing [
3H] WB4101 and [
3H] DHA binding to α
1- and β-receptors, respectively. Scatchard analysis of [
3H] clonidine binding to cortical membranes showed that DA increased the Bmax in both high- and low-affinity components. The increasing effect of DA on [
3H] clonidine binding was dependent on incubation time and temperature, and it was antagonized by pimozide and cis-flupenthixol. The addition of GTP produced a reduction in DA-induced elevation in [
3H] clonidine binding, while that of cyclic AMP did not affect the effect of DA. DA and Mn
2+, though both of them increased [
3H] clonidine binding, appeared to act at a different site in the membrane. Furthermore, the DA-induced increase in [
3H] clonidine binding was found uniformly in membranes prepared from 7 other regions of the rat brain. These results suggested that DA regulates specifically α
2-receptor density by stimulating D
1-receptors and/or via other mechanism(s).
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