Is there a connection between high affinity 3H-spiperone binding sites and DA-sensitive adenylate cyclase in corpus striatum ?

Ca2+‐Guanine Nucleotide Interactions in Brain Membranes. I. Modulation of Central 5‐Hydroxytryptamine Receptors in the Rat

“…According to Snyder and Goodman (1980), the other 5-HT-related sites labelled with ["HIspiperone in the hippocampus and the cerebral cortex should correspond to another class of 5-HT receptors called 5-HT2 since, in their study, the binding of 5-HT agonists to [JH]spiperone sites was not affected by GTP. However, more recent data (Hamon et al, 1980;Marchais and Bockaert, 1980;Rosenfeld and Makman, 1981) clearly indicate that G T P [and P,y-imidoguanosine 5'-triphosphate (GppNHp)] partially inhibits the binding of 5-HT agonists to specific sites labelled with [3H]spiperone both in the striatum and cerebral cortex. In any case, the inhibition of agonist binding to specific sites by guanine nucleotides is never sufficient to lead to the conclusion that these sites belong to receptors coupled to adenylate cyclase (see Marchais and Bockaert, 1980;Rodbell, 1980;Zukin et al, 1980).…”

“…However, more recent data (Hamon et al, 1980;Marchais and Bockaert, 1980;Rosenfeld and Makman, 1981) clearly indicate that G T P [and P,y-imidoguanosine 5'-triphosphate (GppNHp)] partially inhibits the binding of 5-HT agonists to specific sites labelled with [3H]spiperone both in the striatum and cerebral cortex. In any case, the inhibition of agonist binding to specific sites by guanine nucleotides is never sufficient to lead to the conclusion that these sites belong to receptors coupled to adenylate cyclase (see Marchais and Bockaert, 1980;Rodbell, 1980;Zukin et al, 1980). In fact, in studies in newborn rats, we have shown that the high-affinity binding sites for PHIS-HT (which are identical to those found in the brain of adult animals, Nelson et al, 1 9 8 0~) exhibit several characteristics that differ markedly from those of 5-HT receptors coupled to adenylate cyclase (Nelson et al, 1980a,b;Hamon et al, 1980).…”

Comparison of the Binding of [3H]Spiperone and [3H]Domperidone in Homogenates of Mammalian Retina and Caudate Nucleus

“…Even more compelling evidence in favour of the view that [3H]spiperone cannot be labelling D1 receptors comes from consideration of basic drug receptor theory, which predicts that when used at subnanomolar concentrations, [3H] spiperone would label less than 1% of the D1 sites for which it possesses an affinity of approximately 100 nM. Furthermore, the recent studies of Marchais and Bockaert (1980) show that in rat striatum, the dopamine-sensitive adenylate cyclase response, which can be inhibited by haloperidol and spiperone at anticipated K i values, still persists in the presence of a concentration of phenoxybenzamine which will J . Neurochem., Vol.…”