PMID- 28427767
OWN - NLM
STAT- MEDLINE
DCOM- 20170619
LR  - 20180109
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 487
IP  - 2
DP  - 2017 May 27
TI  - beta-arrestins negatively control human adrenomedullin type 1-receptor 
      internalization.
PG  - 438-443
LID - S0006-291X(17)30759-3 [pii]
LID - 10.1016/j.bbrc.2017.04.083 [doi]
AB  - Adrenomedullin (AM) is a potent hypotensive peptide that exerts a powerful 
      variety of protective effects against multiorgan damage through the AM type 1 
      receptor (AM(1) receptor), which consists of the calcitonin receptor-like 
      receptor (CLR) and receptor activity-modifying protein 2 (RAMP2). Two beta-arrestin 
      (beta-arr) isoforms, beta-arr-1 and beta-arr-2, play a central role in the agonist-induced 
      internalization of many receptors for receptor resensitization. Notably, 
      beta-arr-biased agonists are now being tested in phase II clinical trials, targeting 
      acute pain and acute heart failure. Here, we examined the effects of beta-arr-1 and 
      beta-arr-2 on human AM(1) receptor internalization. We constructed a V5-tagged 
      chimera in which the cytoplasmic C-terminal tail (C-tail) of CLR was replaced 
      with that of the beta(2)-adrenergic receptor (beta(2)-AR), and it was transiently 
      transfected into HEK-293 cells that stably expressed RAMP2. The cell-surface 
      expression and internalization of the wild-type or chimeric receptor were 
      quantified by flow cytometric analysis. The [(125)I]AM binding and the AM-induced 
      cAMP production of these receptors were also determined. Surprisingly, the 
      coexpression of beta-arr-1 or -2 resulted in significant decreases in AM(1) receptor 
      internalization without affecting AM binding and signaling prior to receptor 
      internalization. Dominant-negative (DN) beta-arr-1 or -2 also significantly 
      decreased AM-induced AM(1) receptor internalization. In contrast, the AM-induced 
      internalization of the chimeric AM(1) receptor was markedly augmented by the 
      cotransfection of beta-arr-1 or -2 and significantly reduced by the coexpression of 
      DN-beta-arr-1 or -2. These results were consistent with those seen for beta(2)-AR. 
      Thus, both beta-arrs negatively control AM(1) receptor internalization, which 
      depends on the C-tail of CLR.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Kuwasako, Kenji
AU  - Kuwasako K
AD  - Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, 
      Japan. Electronic address: kuwasako@med.miyazaki-u.ac.jp.
FAU - Kitamura, Kazuo
AU  - Kitamura K
AD  - Division of Circulation and Body Fluid Regulation, Faculty of Medicine, 
      University of Miyazaki, Miyazaki 889-1692, Japan.
FAU - Nagata, Sayaka
AU  - Nagata S
AD  - Division of Circulation and Body Fluid Regulation, Faculty of Medicine, 
      University of Miyazaki, Miyazaki 889-1692, Japan.
FAU - Sekiguchi, Toshio
AU  - Sekiguchi T
AD  - Noto Marine Laboratory, Institute of Nature and Environmental Technology, 
      Division of Marine Environmental Studies, Kanazawa University, Ishikawa 927-0553, 
      Japan.
FAU - Danfeng, Jiang
AU  - Danfeng J
AD  - Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, 
      Japan.
FAU - Murakami, Manabu
AU  - Murakami M
AD  - Department of Pharmacology, Hirosaki University, Graduate School of Medicine, 
      Hirosaki 036-8562, Japan.
FAU - Hattori, Yuichi
AU  - Hattori Y
AD  - Department of Molecular and Medical Pharmacology, Graduate School of Medicine and 
      Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
FAU - Kato, Johji
AU  - Kato J
AD  - Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170417
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (ARRB1 protein, human)
RN  - 0 (CALCRL protein, human)
RN  - 0 (Calcitonin Receptor-Like Protein)
RN  - 0 (Receptors, Adrenomedullin)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (beta-Arrestin 1)
RN  - 0 (beta-Arrestin 2)
RN  - 148498-78-6 (Adrenomedullin)
SB  - IM
EIN - Biochem Biophys Res Commun. 2017 Aug 26;490(3):1139. PMID: 28610829
MH  - Adrenomedullin/*metabolism
MH  - Calcitonin Receptor-Like Protein/*metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Receptors, Adrenomedullin/*metabolism
MH  - Receptors, G-Protein-Coupled/*metabolism
MH  - beta-Arrestin 1/*metabolism
MH  - beta-Arrestin 2/*metabolism
OTO - NOTNLM
OT  - Adrenomedullin
OT  - Calcitonin receptor-like receptor
OT  - Receptor activity-modifying protein 2
OT  - Receptor trafficking
OT  - Signal transduction
OT  - beta-arrestins
EDAT- 2017/04/22 06:00
MHDA- 2017/06/20 06:00
CRDT- 2017/04/22 06:00
PHST- 2017/04/08 00:00 [received]
PHST- 2017/04/16 00:00 [accepted]
PHST- 2017/04/22 06:00 [pubmed]
PHST- 2017/06/20 06:00 [medline]
PHST- 2017/04/22 06:00 [entrez]
AID - S0006-291X(17)30759-3 [pii]
AID - 10.1016/j.bbrc.2017.04.083 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2017 May 27;487(2):438-443. doi: 
      10.1016/j.bbrc.2017.04.083. Epub 2017 Apr 17.