Effect of guanine nucleotides on striatal dopamine receptors.

Abstract

GUANINE NUCLEOTIDES have been shown to regulate the sensitivity of adenylate cyclase to hormones in several systems1–5, including the dopamine-sensitive adenylate cyclase in the caudate nucleus2,4. It has also been reported that in the presence of GTP the affinities of glucagon receptors6, β-adrenergic receptors7,8, prostaglandin E1 receptors9 and opiate receptors10 for agonists are decreased. For β-adrenergic receptors this effect of GTP has been described as ‘agonist-specific’, as it is seen with agonists but not with antagonists7,8. We report here a similar effect of GTP on the ability of dopamine-receptor agonists to compete for 3H-spiroperidol binding sites on rat striatal membranes. The presence of 0.3 mM GTP led to a four-to-fivefold increase in the Kd values for the inhibition of 3H-spiroperidol binding by dopamine-receptor agonists. No changes in Kd values were observed for antagonists. Dopamine-receptor agonists and antagonists have been defined by the stimulation or inhibition of dopamine-sensitive adenylate cyclase in the neostriatum11,12 or by their effects on the canine renal artery13. Controversy exists, however, as to whether binding studies using labelled neuroleptics such as spiroperidol actually measure dopamine receptors. Our finding of an agonist-specific effect of GTP supports the conclusion that 3H-spiroperidol is binding to functional dopamine receptors in the caudate nucleus.