Hk. Happe et al., Alpha-2 adrenergic receptor functional coupling to G proteins in rat brainduring postnatal development, J PHARM EXP, 288(3), 1999, pp. 1134-1142
Citations number
40
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
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.