Pw. Mantyh et al., RAPID ENDOCYTOSIS OF A G-PROTEIN-COUPLED RECEPTOR - SUBSTANCE-P-EVOKED INTERNALIZATION OF ITS RECEPTOR IN THE RAT STRIATUM IN-VIVO, Proceedings of the National Academy of Sciences of the United Statesof America, 92(7), 1995, pp. 2622-2626
Studies on cultured cells have shown that agonists induce several type
s of G protein-coupled receptors to undergo internalization. We have i
nvestigated this phenomenon in rat striatum, using substance P (SP)-in
duced internalization of the SP receptor (SPR) as our model system. Wi
thin 1 min of a unilateral striatal injection of SP in the anesthetize
d rat, nearly 60% of the SPR-immunoreactive neurons within the injecti
on zone display massive internalization of the SPR-i.e., 20-200 SPR(+)
endosomes per cell body, Within the dendrites the SPR undergoes a str
iking translocation from the plasma membrane to endosomes, and these d
endrites also undergo a morphological reorganization, changing from a
structure of rather uniform diameter to one characterized by large, sw
ollen varicosities connected by thin fibers, In both cell bodies and d
endrites the number of SPR(+) endosomes returns to baseline within 60
min of SP injection, The number of neurons displaying substantial endo
somal SPR internalization is dependent on the concentration of injecte
d SP, and the SP-induced SPR internalization is inhibited by the nonpe
ptide neurokinin 1 receptor antagonist RP-67,580. These data demonstra
te that in the central nervous system in vivo, SP induces a rapid and
widespread SPR internalization in the cell bodies and dendrites and a
structural reorganization of the dendrites. These results suggest that
many of the observations that have been made on the internalization a
nd recycling of G protein-coupled receptors in in vitro transfected ce
ll systems are applicable to similar events that occur in the mammalia
n central nervous system in vivo.