Alpha-2 adrenergic receptor functional coupling to G proteins in rat brainduring postnatal development

During postnatal development, alpha-2 adrenergic receptors (A2AR) change in both density and distribution. In forebrain, receptor density increases ab out 4-fold over neonatal levels, reaching adult levels before postnatal day (P) 28, whereas in hindbrain, including cerebellum, there is a decrease in overall receptor density. We examined the coupling of A2AR to G proteins u sing agonist-stimulated [S-35]GTP gamma S binding as a functional assay. In forebrain the A2AR agonist-stimulated [S-35]GTP gamma S binding increases rapidly after P7, reaching its highest levels at P21 and then declining sli ghtly to adult levels. This binding increases more slowly than receptor num ber, suggesting that the appearance of G proteins, rather than the A2AR, de termines the developmental appearance of functional A2AR-G protein interact ions in forebrain. Basal [S-35]GTP gamma S binding and [S-35]GTP gamma S bi nding stimulated by other neurotransmitter receptor systems (GABA-B, mu opi ate, and musca-rinic) increase with a time course similar to A2AR-stimulate d [S-35]GTP gamma S binding. In contrast, in hindbrain, A2AR-stimulated [S- 35]GTP gamma S binding decreases during postnatal development in parallel w ith the decrease in A2AR levels, whereas [S-35]GTP gamma S binding stimulat ed by other neurotransmitter receptor systems increases in parallel with ba sal [S-35]GTP gamma S binding. Functional receptor-G protein coupling in hi ndbrain appears to be dependent on the developmental appearance of G protei ns for most neurotransmitter systems. However, for A2AR the decrease in rec eptor density is the overriding factor. These studies 1) demonstrate the fu nctional measurement of A2AR-G protein coupling in native tissue for the fi rst time, 2) demonstrate that A2AR are coupled to G proteins throughout pos tnatal development, and 3) describe developmental increases and decreases i n functional A2AR in brain.