Postnatal development of striatal dopamine function. I. An examination of D1 and D2 receptors, adenylate cyclase regulation and presynaptic dopamine markers.
We have characterized the postnatal development from 1 to 7 weeks after birth in rat striatal homogenates of D1 and D2 dopamine (DA) receptor sites, adenylate cyclase (AC) enzyme activity coupled to DA receptor function, guanine nucleotide binding sites and presynaptic markers of DA terminal function. D1 receptor density, expressed per unit of membrane protein, does not increase over this developmental interval, while maximum DA-stimulated AC activity per mg membrane protein increases 50-100%. D1 agonist affinity for D1 receptor sites doubles by 7 weeks of age but is consistently reduced by guanine nucleotide during development. Guanine nucleotide stimulation of AC develops a biphasic dose-response curve after 3 weeks of age. Between 2 and 4 weeks postnatal age there is a rapid increase in AC catalytic component activity as manifested by the capacity of forskolin or manganese ion to stimulate AC in presence of guanine nucleotide and DA. Reversible [3H]GppNHp (guanyldiphosphonateimidophosphate) binding to striatal homogenates is dependent on Mg2+, inhibited by Ca2+ and GppNHp analogues, and occurs in about a 300-fold excess over D1 sites. Presynaptic markers of dopaminergic function indicate a 7-fold increase in tissue DA levels, a 2-fold reduction in DA turnover and no apparent change in density of DA uptake sites, assayed by [3H]mazindol binding. Subcomponents of D1 and D2 DA receptors have distinct postnatal developmental profiles. Striatal D1 sites do not change significantly during development, but D2 receptors and GTP inhibition of AC increase and appear, respectively, at 3-4 weeks of age, at the same time as the massive matrix innervation of striatum by DA terminals.
Broaddus
W C
WC
Department of Neurological Surgery, University of Virginia School of Medicine, Charlottesville 22908.
Bennett
J P
JP
D000262:Adenylyl Cyclases / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D003342:Corpus Striatum / Q000254:growth & development / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism* / Q000502:physiology
D011954:Receptors, Dopamine; D006165:Guanylyl Imidodiphosphate; D000262:Adenylyl Cyclases; D004298:Dopamine