Vol. 54, Issue 2, 231-232, June 2002
International Union of Pharmacology. XXXI. Recommendations for
the Nomenclature of Multimeric G Protein-Coupled Receptors
M.
Spedding,
T. I.
Bonner and
S. P.
Watson
Institut de Recherches Internationales Servier (I.R.I.S.),
Neuilly-sur-Seine Cedex, France (M.S.); Laboratory of Genetics,
National Institute of Mental Health, Bethesda, Maryland (T.I.B.); and
Department of Pharmacology, University of Oxford, Oxford, United
Kingdom (S.P.W.)
Abstract
I. Introduction
II. 
-Aminobutyric AcidB Receptor Family
III. Calcitonin Receptor Family
IV. Conclusions
References
 |
Abstract |
A receptor is defined by the International Union of
Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) as a protein, or a complex of proteins, which recognizes physiologically relevant ligands that can regulate the protein to
mediate cellular events (Ruffolo et al., 2000
). This definition does
not include associated proteins, which are not required for agonist
recognition and/or receptor assembly. Thus, G proteins are not included
in the nomenclature of G protein-coupled receptors (GPCRs). Similarly,
proteins which modify receptor disposition, such as proteins with a PDZ
domain (Sheng and Sala, 2001), and which associate with the cytosolic
portion of the receptor are not included. The question arises, however,
as to the way to name multimeric receptors where subunits influence
receptor assembly and agonist recognition. The essential issue is
whether to name the individual proteins or the association of proteins?
NC-IUPHAR recommends that, where possible, the functional receptor
complex be given a different name from that of the subunits.
| |
I. Introduction |
In this issue of Pharmacological Reviews, two families
of GPCRs are considered where a modulatory protein
influences agonist binding. The two cases are distinct. The
GABAB family consists of two seven-transmembrane
proteins that are believed to function in vivo only as a heterodimer.
There is no evidence for more than one receptor within this family. The
calcitonin receptor family also consists of two seven-transmembrane
proteins, but here the receptor pharmacology is influenced by the
existence of single-transmembrane domain proteins, termed receptor
activity modifying proteins (RAMPs). The NC-IUPHAR subcommittee on
calcitonin receptors presently recognizes seven receptors within this family.
| |
II.  -Aminobutyric AcidB Receptor Family |
In the case of the GABAB receptor, the
GABAB1 subunit acts as the acceptor protein for
the agonist, and the structurally similar GABAB2
subunit is necessary for transport of the receptor to the cell surface
and G protein activation. The NC-IUPHAR subcommittee on
GABAB receptors finds no clear evidence for
multiple types of the GABAB receptor. Therefore,
the multimeric receptor is referred to as a GABAB
receptor, made up of GABAB1 and
GABAB2 subunits (Bowery et al., 2002).
| |
III. Calcitonin Receptor Family |
In the second case (Poyner et al., 2002), the pharmacology of the
two related seven-transmembrane proteins is influenced by the
expression of three RAMPs. The two seven-transmembrane components are
known as the calcitonin (CT) receptor and the calcitonin-like (CL)
receptor. CT is functional when expressed on its own and serves as a
receptor for calcitonin. However, in the presence of RAMP1, 2, or 3, CT
also becomes a receptor for amylin as well as calcitonin
with each
complex having a unique pharmacology. Each receptor complex is given a
separate name although they probably co-exist as a mixed population.
They are named AMY1, AMY2,
and AMY3 corresponding to RAMP1, 2, and 3, respectively, to reflect the fact that all respond to amylin. In
addition, they also respond in varying degrees to calcitonin but this
nomenclature enables distinction with the CT receptor, which
only responds to calcitonin. CL is only functional when
complexed with RAMP1, 2, or 3. The complex of CL and RAMP1 is known as
the CGRP (calcitonin gene-related peptide) receptor, whereas a complex
of CL and RAMP2 or RAMP3 are known as AM1 and
AM2 receptors, respectively, to reflect the fact
that they respond to adrenomedullin.
Nevertheless, in systems where an accessory protein may change the
pharmacology of an agonist, caution should be exercised, because
different degrees of protein expression may markedly modify responses
and apparent receptor distribution.
| |
IV. Conclusions |
The definition of a receptor, at the level of either a single
protein or an association of proteins, allows a pragmatic approach to
classification, which is the only approach possible in the face of
combinatorial association of multiple subunits. NC-IUPHAR will use this
same approach in naming other receptor classes, including ion channels
and nuclear receptors. The decision to base the classification at the
level of the single protein, or the association of proteins, is
dependent on many different parameters, the importance of which depends
on the receptor class in question.
| |
Footnotes |
Address correspondence to: Pr. Michael Spedding, Institut de
Recherches Internationales Servier (I.R.I.S.), 192 avenue Charles de
Gaulle, 92578 Neuilly-sur-Seine cedex, France. E-mail:
michael.spedding{at}fr.netgrs.com
| |
Abbreviations |
GPCRs, G protein-coupled
receptors;
GABA, 
-aminobutyric acid;
RAMPs, receptor activity
modifying proteins;
NC-IUPHAR, International Union of Pharmacology
Committee on Receptor Nomenclature and Drug Classification;
CT, calcitonin;
CL, calcitonin-like;
AMY, amylin;
AM, adrenomedullin.
| |
References |
-
Bowery NG,
Bettler B,
Froestl W,
Gallagher JP,
Marshall F,
Raiteri M,
Bonner TI and
Enna SJ
(2002)
International Union of Pharmacology. XXXIII. Mammalian GABAB receptors: structure and function.
Pharmacol Rev
54:
247-264[Abstract/Free Full Text].
-
Poyner DR,
Sexton PM,
Marshall I,
Smith DM,
Quirion R,
Born W,
Muff R,
Fischer JA and
Foord SM
(2002)
International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors.
Pharmacol Rev
54:
233-246[Abstract/Free Full Text].
-
Ruffolo RR,
Humphrey PPA,
Watson SP and
Spedding M
(2000)
Revised NC-IUPHAR recommendations for nomenclature of receptors, in
The IUPHAR Compendium of Receptor Characterization and Classification 2nd ed pp 7-8,
IUPHAR Media, London, UK.
-
Sheng M and
Shala C
(2001)
PDZ domains and the organization of supramolecular complexes.
Annu Rev Neurosci
24:
1-29[CrossRef][Medline].
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