RAPID ENDOCYTOSIS OF A G-PROTEIN-COUPLED RECEPTOR - SUBSTANCE-P-EVOKED INTERNALIZATION OF ITS RECEPTOR IN THE RAT STRIATUM IN-VIVO

Citation
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
Citations number
32
Categorie Soggetti
Multidisciplinary Sciences
ISSN journal
00278424
Volume
92
Issue
7
Year of publication
1995
Pages
2622 - 2626
Database
ISI
SICI code
0027-8424(1995)92:7<2622:REOAGR>2.0.ZU;2-T
Abstract
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.