Ontogenetic Development of the Striatal [³H]Spiperone Binding: Regulation by Sodium and Guanine Nucleotide in Rats

Abstract

Ontogenetic development of specific [3H]spiperone binding to crude synaptic membranes and its regulation by Na+ and GTP was investigated in the rat striatum. (d)-Butaclamol more effectively inhibited [3H]spiperone binding than (l)-butaclamol. The ratio of inhibitory activity of (d)- and (l)-butaclamol for [3H]spiperone binding was not different between 1-, 7-, and 70-day-old animals but eight- to ninefold lower at 18 days of gestation than during the postnatal period. A Scatchard plot of specific binding indicated the presence of two types of binding: low-affinity (KD = 1.51 nM) and high-affinity (KD = 0.09 nM) binding on day 70. Only one component (KD = 0.075 nM) was observed on days 1 and 7 and both types of binding were found on day 15. Bmax gradually increased with age and reached a peak on day 30, followed by a decline on days 70 and 360. Na+, 100 mM, significantly increased specific binding on days 1, 7, 15, and 70. GTP, 50 microM, completely reversed the Na+-induced decrease in IC50 of apomorphine on both days 15 and 70, but not on day 7. It is suggested that receptors could recognize ligand stereospecificity on day 1. The density in dopamine receptors in the striatum reaches a peak on day 30, followed by a decrease on days 70 and 360. In addition, regulation by Na+ and GTP in agonist binding to dopamine receptors seems to become functional between 1 and 2 weeks after birth.

Human brain dopamine receptors in children and aging adults

“…In animals, the D1 density usually remains constant with age (Govoni et al, 1978;Henry et al, 1986;O'Boyle and Waddington, 1984;Rosengarten et al, 19851, while the Dz density falls (Henry et al, 1986;Nomura et al, 1982;Pardo et al, 1977;Severson and Finch, 1980a,b;Severson and Randall, 1985). In human tissues, the data relating D2 density and age are conflicting.…”

Solubilization of D2 Dopamine Receptor Coupled to Guanine Nucleotide Regulatory Protein from Bovine Striatum

“…The DZtype dopamine receptor is considered to be responsible for the behavioral and clinical effects of neuroleptics (Seeman, 1980). Many hormone and neurotransmitter receptors, including the Dz dopamine receptor, are regulated by guanine nucleotides (Creese et al, 1979;Rodbell, 1980;Freedman et al, 1981;Nomura et al, 1982). These effects are thought to involve a GTP binding protein that is separate from the receptor recognition protein.…”

Effects of adenosine on cAMP production during early development in the optic tectum of chicks

“…These differences may be due to a distinct degree of expression or availability of receptors,5,7, 51 or to variations of receptor affinities. 26,31,33 We have observed that cAMP accumulation induced by adenosine in young rat brain slices was lower than in adult rats (data not shown), but other studies have shown that adenosine receptors increase with brain development.ll, 13,26 Alternatively, the decline in stimulation may be related to ontogenetic alterations in the coupling of the components of the receptor/G protein/adenylate cyclase system. 11,15,16,20,25,26,32 Another possibility could be a variation in PDE activity during development.…”