The extracellular calcium-sensing receptor is expressed in rat microglia and modulates an outward K+ channel

被引:40
作者
Chattopadhyay, N
Ye, CP
Yamaguchi, T
Nakai, M
Kifor, O
Vassilev, PM
Nishimura, RN
Brown, EM
机构
[1] Brigham & Womens Hosp, Dept Med, Div Endocrine Hypertens, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA USA
[3] Vet Adm Med Ctr, Res Serv, Dept Neurol, Sepulveda, CA 91343 USA
[4] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA
[5] Hyogo Inst Aging Brain & Cognit Disorders, Himeji, Hyogo, Japan
关键词
calcium; calcium-sensing receptor; microglial function;
D O I
10.1046/j.1471-4159.1999.0721915.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The calcium-sensing receptor (CaR) is a G protein-coupled receptor that "senses" extracellular calcium ions (Ca-o(2+)) as an extracellular first messenger. In this report, we have shown that the CaR is expressed in primary cultures of microglial cells derived from rat brain as assessed by RT-PCR using four CaR-specific primer pairs followed by sequencing of the amplified products, by northern blot analysis using a CaR-specific probe, as well as by immunocytochemistry and western analysis utilizing a specific polyclonal anti-CaR antiserum. In addition, raising Ca-o(2+) from 0.75 to 3.0 mM or addition of the polycationic CaR agonist neomycin or a "calcimimetic" CaR activator (R-467; NPS Pharmaceuticals) increased the open state probability (P-o) of a Ca+-activated K+ channel having a unitary conductance of 84 +/- 4 pS, indicating that the channel is modulated by the CaR, Therefore, our data strongly suggest that a functional CaR is expressed in cultured rat microglia, similar to that in parathyroid gland and kidney, which could potentially play an important role(s) in regulating microglial function.
引用
收藏
页码:1915 / 1922
页数:8
相关论文
共 36 条
[1]   Expression and characterization of inactivating and activating mutations in the human Ca-0(2+)-sensing receptor [J].
Bai, M ;
Quinn, S ;
Trivedi, S ;
Kifor, O ;
Pearce, SHS ;
Pollak, MR ;
Krapcho, K ;
Hebert, SC ;
Brown, EM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (32) :19537-19545
[2]   A SUBPOPULATION OF BONE MARROW-DERIVED MACROPHAGE-LIKE CELLS SHARES A UNIQUE ION CHANNEL PATTERN WITH MICROGLIA [J].
BANATI, RB ;
HOPPE, D ;
GOTTMANN, K ;
KREUTZBERG, GW ;
KETTENMANN, H .
JOURNAL OF NEUROSCIENCE RESEARCH, 1991, 30 (04) :593-600
[3]   CLONING AND CHARACTERIZATION OF AN EXTRACELLULAR CA2+-SENSING RECEPTOR FROM BOVINE PARATHYROID [J].
BROWN, EM ;
GAMBA, G ;
RICCARDI, D ;
LOMBARDI, M ;
BUTTERS, R ;
KIFOR, O ;
SUN, A ;
HEDIGER, MA ;
LYTTON, J ;
HEBERT, SC .
NATURE, 1993, 366 (6455) :575-580
[5]   Calcium-sensing receptor in the rat hippocampus: A developmental study [J].
Chattopadhyay, N ;
Legradi, G ;
Bai, M ;
Kifor, O ;
Ye, CP ;
Vassilev, PM ;
Brown, EM ;
Lechan, RM .
DEVELOPMENTAL BRAIN RESEARCH, 1997, 100 (01) :13-21
[6]  
Chattopadhyay N, 1998, GLIA, V24, P449, DOI 10.1002/(SICI)1098-1136(199812)24:4<449::AID-GLIA10>3.3.CO
[7]  
2-0
[8]   Identification and localization of extracellular Ca2+-sensing receptor in rat intestine [J].
Chattopadhyay, N ;
Cheng, I ;
Rogers, K ;
Riccardi, D ;
Hall, A ;
Diaz, R ;
Hebert, SC ;
Soybel, DI ;
Brown, EM .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 1998, 274 (01) :G122-G130
[9]   Ca2+ receptor from brain to gut:: Common stimulus, diverse actions [J].
Chattopadhyay, N ;
Yamaguchi, T ;
Brown, EM .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 1998, 9 (09) :354-359
[10]   THE ROLE OF POTASSIUM CHANNELS IN SCHWANN-CELL PROLIFERATION IN WALLERIAN DEGENERATION OF EXPLANT RABBIT SCIATIC-NERVES [J].
CHIU, SY ;
WILSON, GF .
JOURNAL OF PHYSIOLOGY-LONDON, 1989, 408 :199-222