Development of A1 adenosine receptors in the chick embryo retina.
Adenosine inhibits cyclic AMP synthesis induced by dopamine in embryonic but not in post-hatched chick retinas. N6-Cyclohexyladenosine (CHA), which preferentially activates A1 receptors as well as 2-chloroadenosine, inhibits cyclic AMP accumulation induced by dopamine in retinas from 10-day-old embryos (E10) with IC50's of 0.1 and 0.5 microM, respectively, but this effect is not detectable after hatching. In order to verify if this developmental change reflects variations in the number or affinity of A1 adenosine receptors, their development during chick retina ontogeny was studied. Binding studies using 3(H)CHA revealed the presence of A1 receptors at all stages of development examined, including the post-hatched retina. The number of binding sites increased between E10 and E17, and then decreased in post-hatched animals. In the latter, 3(H)CHA binding was to a single site with a Bmax of 128.6 +/- 13.4 fmol/mg protein and a Kd of 2.1 + 0.2 nM. Various ligands showed similar hierarchies of affinity for the A1 receptor in embryonic and post-hatched retinas, namely, CHA greater than R-N6-phenylisopropyladenosine (1-PIA) greater than 5'-N-ethylcarboxamideadenosine (NECA) greater than isobuthylemethyl-xanthine (IBMX). Given that CHA inhibited forskolin-induced cyclic AMP production and Gpp(NH)p inhibited 3(H)CHA binding in both embryonic and post-hatched retinas, it appears that receptor coupling to adenylate cyclase is present since early embryonic stages. The results suggest that the A1 receptors may have different functions in the embryonic as compared to the mature chick retina.
Paes de Carvalho
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Department of Neurobiology, Federal Fluminense University, Niteroi, Brazil.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002642:Chick Embryo; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology; D005314:Embryonic and Fetal Development; D011983:Receptors, Purinergic / Q000378:metabolism* / Q000502:physiology; D012160:Retina / Q000196:embryology / Q000378:metabolism*
D011983:Receptors, Purinergic; C027513:N(6)-cyclohexyladenosine; D000242:Cyclic AMP; D000241:Adenosine; D004298:Dopamine