Dopamine receptors in human foetal brains: characterization, regulation and ontogeny of [3H]spiperone binding sites in striatum.
Eighteen corpora striata from normal human foetal brains ranging in gestational age from 16 to 40 weeks and five from post natal brains ranging from 23 days to 42 years were analysed for the ontogeny of dopamine receptors using [3H]spiperone as the ligand and 10 mM dopamine hydrochloride was used in blanks. Spiperone binding sites were characterized in a 40-week-old foetal brain to be dopamine receptors by the following criteria: (1) It was localized in a crude mitochondrial pellet that included synaptosomes; (2) binding was saturable at 0.8 nM concentration; (3) dopaminergic antagonists spiperone, haloperidol, pimozide, trifluperazine and chlorpromazine competed for the binding with IC50 values in the range of 0.3-14 nM while agonists--apomorphine and dopamine gave IC50 values of 2.5 and 10 microM, respectively suggesting a D2 type receptor. Epinephrine and norepinephrine inhibited the binding much less efficiently while mianserin at 10 microM and serotonin at 1 mM concentration did not inhibit the binding. Bimolecular association and dissociation rate constants for the reversible binding were 5.7 x 10(8) M-1 min-1 and 5.0 x 10(-2) min-1, respectively. Equilibrium dissociation constant was 87 pM and the KD obtained by saturation binding was 73 pM. During the foetal age 16 to 40 weeks, the receptor concentration remained in the range of 38-60 fmol/mg protein or 570-1080 fmol/g striatum but it increased two-fold postnatally reaching a maximum at 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)
Kumar
B V
BV
Department of Biochemistry, Indian Institute of Science, Bangalore.
Sastry
P S
PS
D000328:Adult; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D002675:Child, Preschool; D003342:Corpus Striatum / Q000196:embryology*; D004298:Dopamine / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D011954:Receptors, Dopamine / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism* / Q000494:pharmacology; D014316:Tritium
D011954:Receptors, Dopamine; D014316:Tritium; D013134:Spiperone; D006160:Guanosine Triphosphate; D004298:Dopamine