Brain maturation of high-affinity adenosine A2 receptors and their coupling to G-proteins.
The neuromodulator adenosine is acting through specific receptors, A1 and A2, coupled to their effector systems via G-proteins. The regulatory effects of adenosine on locomotor activity have been attributed to an interaction with A2 striatal receptors. The postnatal development of adenosine A2a receptors was analysed in rat striatal membranes and by quantitative autoradiography in brain sections using [3H]CGS 21680 as specific probe. At the concentration of radioligand used (5 nM), A2a sites were concentrated in the striatum at all ages, with minor developmental alterations in the expression pattern within the striatal regions. In membrane preparations, Scatchard analysis showed that the density of CGS 21680 binding sites was low at birth, around 3% of the adult value, and then increased, mostly between birth and 5 days and then from 15 days to adulthood. Concomitantly, the receptor affinity decreased sharply during brain development, Kd values varying from 2 to 15.5 nM. The addition of a GTP analogue, guanylyl-5'-imidodiphosphate (Gpp(NH)p, 10 microM), to the assay medium reduced significantly the receptor affinity throughout the postnatal development, reflecting a coupling to G-proteins at all ages, but it also suggested a weaker association at birth. These data show that the developmental properties of A2a receptors contrast with those of A1 receptors, and emphasize the role played by adenosine through its A2 receptors in the maturation of striatum-related cerebral pathways.
Doriat
J F
JF
INSERM U.272, Université de Nancy, France.
Humbert
A C
AC
Daval
J L
JL
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001345:Autoradiography; D001667:Binding, Competitive / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008297:Male; D017072:Neostriatum / Q000737:chemistry* / Q000254:growth & development; D010627:Phenethylamines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000032:analysis / Q000378:metabolism*; D014316:Tritium
D000959:Antihypertensive Agents; D010627:Phenethylamines; D018047:Receptors, Purinergic P1; D014316:Tritium; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D006165:Guanylyl Imidodiphosphate; D019204:GTP-Binding Proteins; D000241:Adenosine