Quantitative autoradiographic study of the postnatal development of adenosine A1 receptors and their coupling to G proteins in the rat brain.
Adenosine is now considered as a major regulatory agent in the mammalian central nervous system. Its actions are mediated by specific receptors which are coupled with an adenylate cyclase system via a G protein. The postnatal development of adenosine A1 receptors was studied by quantitative autoradiography using [3H]N6-cyclohexyladenosine, a potent receptor agonist in 42 rat brain structures. The coupling of these sites to G proteins was examined by measuring the effects of in vitro addition of guanylyl-5'-imidodiphosphate, a stable analogue of guanosine triphosphate, on N6-cyclohexyladenosine binding. [3H]N6-Cyclohexyladenosine-specific binding was quite low at birth, around 10% of adult levels, and exhibited a rather homogeneous distribution pattern, except in thalamic nuclei. Data showed a sequential development of adenosine A1 receptors in relation to the time course of maturation of cerebral structures with a proliferation peak which paralleled rapid brain growth. The time period by which adult levels are reached differed according to the cerebral region studied. N6-Cyclohexyladenosine-specific binding sites appeared to be functionally linked to G proteins in all structures and at all postnatal stages. However, the potency of guanylyl-5'-imidodiphosphate to displace N6-cyclohexyladenosine binding was significantly lower before 5 days of age, suggesting functional changes during postnatal maturation in cerebral pathways modulated by adenosine.
Daval
J L
JL
INSERM U.272, Nancy, France.
Werck
M C
MC
Nehlig
A
A
Pereira de Vasconcelos
A
A
D000241:Adenosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000254:growth & development*; D001923:Brain Chemistry; D001931:Brain Mapping; D019204:GTP-Binding Proteins / Q000032:analysis*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D051381:Rats; D011983:Receptors, Purinergic / Q000032:analysis*; D015398:Signal Transduction
D011983:Receptors, Purinergic; D006165:Guanylyl Imidodiphosphate; C027513:N(6)-cyclohexyladenosine; D019204:GTP-Binding Proteins; D000241:Adenosine