Rapid endocytosis of a G protein-coupled receptor: substance P evoked internalization of its receptor in the rat striatum in vivo.
Studies on cultured cells have shown that agonists induce several types of G protein-coupled receptors to undergo internalization. We have investigated this phenomenon in rat striatum, using substance P (SP)-induced internalization of the SP receptor (SPR) as our model system. Within 1 min of a unilateral striatal injection of SP in the anesthetized rat, nearly 60% of the SPR-immunoreactive neurons within the injection zone display massive internalization of the SPR--i.e., 20-200 SPR+ endosomes per cell body. Within the dendrites the SPR undergoes a striking translocation from the plasma membrane to endosomes, and these dendrites also undergo a morphological reorganization, changing from a structure of rather uniform diameter to one characterized by large, swollen varicosities connected by thin fibers. In both cell bodies and dendrites the number of SPR+ endosomes returns to baseline within 60 min of SP injection. The number of neurons displaying substantial endosomal SPR internalization is dependent on the concentration of injected SP, and the SP-induced SPR internalization is inhibited by the nonpeptide neurokinin 1 receptor antagonist RP-67,580. These data demonstrate 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 and recycling of G protein-coupled receptors in in vitro transfected cell systems are applicable to similar events that occur in the mammalian central nervous system in vivo.
Mantyh
P W
PW
Molecular Neurobiology Laboratory (151), Veterans Administration Medical Center, Minneapolis, MN 55417, USA.
Allen
C J
CJ
Ghilardi
J R
JR
Rogers
S D
SD
Mantyh
C R
CR
Liu
H
H
Basbaum
A I
AI
Vigna
S R
SR
Maggio
J E
JE
D000704:Analysis of Variance; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004705:Endocytosis / Q000187:drug effects*; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D016253:Microscopy, Immunoelectron; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution
D018040:Receptors, Neurokinin-1; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; D019204:GTP-Binding Proteins