Vol. 50, Issue 2, 271-278, June 1998

International Union of Pharmacology. XIX. The IUPHAR Receptor Code: A Proposal for an Alphanumeric Classification System

Glaxo Institute of Applied Pharmacology, Department of Pharmacology (P.P.A.H.), University of Cambridge, Cambridge, England and Molecular Neurobiology Unit, Division of Basic Medical Sciences (E.A.B.), Royal Free Hospital School of Medicine, London, England

I. Rationale for a Receptor Code
II. Criteria for Receptor Characterization
III. Proposal for a Systematic Receptor Code
IV. Conclusions
Acknowledgments
References

	I. Rationale for a Receptor Code

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A generally accepted system for defining, characterizing, and classifying transmitter/hormone receptors is desirable for several reasons. First, pharmacologists need a common language so that ambiguity is not created by varied and inconsistent terminologies. It is estimated that a significant fraction of the mammalian genome codes for receptor proteins and subunits; this leads to the prediction of several thousands of individual signal-transducing receptors, even without consideration of the very large group of olfactory and gustatory receptors that exists (see Glusman et al., 1996). Thus, an internationally acceptable classification system for receptors is both desirable and necessary. Second, the development of a systematic scheme of classification is in itself an important generic research approach in biological science. It can bring focus, highlight relationships, and stimulate the recognition and investigation of features common to various classes and groups. It also can indicate deficiencies in our information and add an evolutionary perspective, which may bring its own insights. It remains to be determined why there is, in many cases, such a large variety of receptors for a given chemical messenger transmitter. We need to determine whether all these receptors are functional. It is also interesting to consider how they evolved and how many more endogenous ligands, known and unknown, are to be anticipated. Third, drug discovery benefits greatly from the systematic analysis of the growing body of information on receptors and their subclassification, with the knowledge that each receptor subtype provides a potential new drug target. Thus, it is now well recognized that the identification of well defined receptor subtypes often leads to highly specific drugs with new clinical indications and/or less undesirable side effects. It is reasonable to assume that future computer-based analyses or predictions of drug selectivities will benefit greatly from an established universal framework of a systematic receptor classification.

The term "receptor" is in use in various broad senses, but for pharmacological purposes the term is used specifically (Barnard, 1997; Humphrey, 1997) and refers to proteins which are "signal transducing receptors," as defined and discussed by Kenakin et al. (1992). That is, each such protein specifically recognizes and is activated by a native agonist, which is one of numerous different messenger molecules that specifically relay a signal into a cell or between compartments within a cell. Thus, receptors in the pharmacological sense may be in one of three locations: (a) in the plasma membrane (the receptors for neurotransmitters, trophins, growth factors, and cytokines, other immunomediators, morphogens, sensory stimulants, and chemoattractants, and circulating hormones); (b) in an organelle membrane (e.g., those receptors where the transduction process involves the release of Ca²⁺ from an intracellular store); (c) in the cytosol. Case c can involve migration of the ligand-bound receptor to the cell nucleus, as for the receptors that belong to the superfamily of ligand-regulated transcription factors, whose ligands are steroid hormones and certain other fat-soluble hormones (structural class 4 here; see below). For all the natural signal-transducing agonists involved, the general term "transmitter" can be used.

As a consequence of the considerations listed above, much effort has been dedicated recently to the classification of the pharmacologically better-known neurotransmitter receptors. However, molecular biology has created a dramatic increase in information on the existence and structure of receptors, often preceding any data on their function, thereby reversing the traditional order of pharmacological data acquisition. The IUPHAR Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), with its various Subcommittees,^b has been constituted to review current approaches to receptor characterization and to define a generic scheme of nomenclature (Vanhoutte et al., 1994, 1996; Humphrey et al., 1994). Although progress has been made in standardizing trivial names in several receptor areas (and this initiative will continue), it is suggested that an all-embracing, rational system of coding receptors should be introduced [an alphanumeric receptor code (RC)^c], analogous to the EC (Enzyme Commission) enzyme codes introduced by the International Union of Biochemistry and Molecular Biology (IUBMB). It will differ from the EC system (which was set up before the era of molecular biology) in that the proposed codes are intended to convey structural information (relevant to the mode of receptor transduction) together with additional elements relating to operational characteristics, set out in a hierarchical order. This should provide a unique, unambiguous, and authoritative descriptor for each receptor protein. Each RC, assigned by NC-IUPHAR, is intended to be used in publications for definitive identification, in conjunction with a suitable (ideally, approved) trivial name. It also will be used in The IUPHAR Compendium of Receptor Characterization and Classification (July 1998), together with the planned IUPHAR Receptor Database which will link uniquely nucleotide and protein databases to comprehensive data on receptor function and drug-related operational characteristics (recognition and transduction).

The details presented here constitute a proposal, sanctioned by NC-IUPHAR (see acknowledgment), which provides a basis for a broad and full debate within the pharmacological community at large and with scientists from other disciplines and their representative bodies.

	II. Criteria for Receptor Characterization

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It generally is acknowledged that studies toward the pharmacological characterization and classification of neurotransmitter/hormone/autacoid receptors should involve work on both function and structure (e.g., see Humphrey et al., 1993, 1994; Vanhoutte et al., 1994; Hoyer et al., 1994; Humphrey, 1997). Receptor structure, in terms of its amino acid sequence, is unambiguous and will allow the allocation of a database code to the unequivocally identified protein. Function is equally important and not necessarily sufficiently predictable from structure, although it may be. Thus, one amino acid difference may make important differences in the drug recognition characteristics of a receptor (cf., the rat and human neurokinin NK₁ receptors) or by contrast significant differences in receptor sequence homology may make little such difference (e.g., in human 5-HT_1B and 5-HT_1D receptors or somatostatin receptors sst₁ and sst₄) (see Sachais et al., 1993; Hoyer et al., 1994, 1995). It is therefore essential to establish which drugs are specific and selective for a particular receptor, either as agonists or antagonists, and to provide appropriate quantitative measurements of key parameters (see Kenakin et al., 1992; Jenkinson et al., 1995). The affinities (as dissociation equilibrium constants) of ligands often are measured from radioligand binding studies, and such data (at least for antagonists) should be equivalent to the corresponding data from functional studies. It has been argued that parameters from both types of studies clearly cannot be considered on semantic grounds under the umbrella term "functional" and hence the term "operational" has been introduced (Humphrey et al., 1994; Humphrey, 1997). Doubts about the use of "operational" in this context have been expressed because of its prior (and currently accepted) use in reference to agonism and agonist-specific parameters, which involve an efficacy component with more than just a binding (and recognition) parameter being involved (Kenakin et al., 1992; Black and Leff, 1983). However, this strengthens the argument for using the term "operation" which, importantly, implies an added involvement of receptor "activation" and hence transduction. The alternative term "recognition" more specifically refers to the binding characteristics or binding affinities of drugs (both agonist and antagonist) for a given receptor but does not necessarily encompass all aspects of receptor function, as the term "operational" undoubtedly does.

Transduction in the context of receptor characterization is intended to refer to the steps that allow the binding of an agonist at the receptor to be linked to the transmission of a signal into a cell or between compartments of a cell. This necessarily will involve specific changes in the receptor protein (if it is in the ion-channel class) or, in other cases, relayed to associated proteins which execute the primary signaling step. Transductional data should not involve the categorization of more downstream second-message cascades themselves, although such information might be used judiciously to infer events upstream. Even if more tightly defined, the use of transductional data to characterize receptors is controversial but it has been invaluable nevertheless in the classification of 5-HT receptors (Humphrey et al., 1993; Hoyer et al., 1994). Thus 5-HT_1C (now called 5-HT_2C) and 5-HT₂ (now called 5-HT_2A) receptors were predicted to belong to the same receptor group on the basis of shared transduction mechanisms. This was confirmed later when both receptor genes were cloned and the respective proteins were shown to share a high degree of homology (Hoyer et al., 1994). In contrast, although both 5-HT₃ and 5-HT₄ receptor types can be blocked by tropisetron (albeit at different concentrations), it was obvious on the basis of transduction that the two receptors were quite distinct even before both genes had been cloned (Humphrey et al., 1993; Hoyer et al., 1994). Thus, at the very least, consideration of the transduction mechanism involved will distinguish between a ligand-gated ion channel receptor and a G protein-coupled receptor (i.e., the 5-HT₃ and 5-HT₄ receptor, respectively). It should be noted that the structural classes proposed here reflect known fundamentally different transduction mechanisms for each. It follows that a knowledge of receptor transduction mechanisms from functional studies is important but how much value should be attached to such operational data specifically for receptor characterization purposes in isolation remains to be determined. However, there is a growing view that the unique intracellular face of each membrane-bound receptor protein will dictate preferred stoichiometric interactions with adjacent proteins, which will be characteristic of the receptor type involved. On the basis of these arguments, essential operational data for receptor characterization would include all drug recognition and drug interaction data, from both functional as well as radioligand binding studies, together with data on receptor transduction mechanisms directly related to receptor activation.

In summary, we propose that the pharmacological criteria for receptor characterization will depend on the integration of data from studies on both receptor structure and receptor operation. When such an integrated pharmacological profile is detailed sufficiently it will be possible to register an IUPHAR RC with confidence.

	III. Proposal for a Systematic Receptor Code

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A systematic numbering system for all known pharmacological receptors allows definitive labeling of a particular receptor by an international pharmacological authority (NC-IUPHAR), while providing valuable classified information about its characteristics. Each RC would provide a unique identifier for each receptor within The NC-IUPHAR Receptor Database, which contains extensive pharmacological information on receptor characterization and classification. This would be analogous to the EC numbering system used for enzymes. If necessary such codes could be changed when new information and understanding dictated that change was essential. A full alphanumeric code could provide a universally accessible record of numbering and subclassification of receptors which would reflect the state of current knowledge for the structure and characteristics of each receptor. The coding system would not replace trivial names, which usually would be used, but it would circumvent some of the problems associated with attempts to standardize such trivial names.

The proposed RC would consist of a set of divisions, separated from each other by full points; each division conveys a different category of information about the receptor, as summarized in table 1. Thus, according to the system proposed, the rat 5-HT_1A receptor (as a G protein-coupled recombinant receptor for 5-HT, classified pharmacologically as the 1A subtype) would have a RC of 2.1.5HT.1A.RNO.00.00 and the human 5-HT₃ (as the first ligand-gated cation channel receptor subunit for 5-HT) would have an RC of 1.1.5HT.01.HSA.00.00.S. Other examples to illustrate the coding system are the rat muscarinic acetylcholine receptor (2.1.ACH.M1.RNO.00.00) and the human P2X₁ receptor subunit (1.4.NUCT.01.HSA.00.00.S). These RCs are based on the assignment of the coded information explained in this document. (See tables 2-8.)

View this table: [in this window] [in a new window]   TABLE 1 Subdivisions within a complete receptor code

View this table: [in this window] [in a new window]   TABLE 2 Main structural class codes

View this table: [in this window] [in a new window]   TABLE 3 Subclasses within structural class 1  (ion-channel receptors)

View this table: [in this window] [in a new window]   TABLE 4 Subclasses within structural class 2  (G protein-coupled receptors)

View this table: [in this window] [in a new window]   TABLE 5 Subclasses within structural class 3  (enzyme-associated single transmembrane domain receptors)

View this table: [in this window] [in a new window]   TABLE 6 Subclasses within structural class 4  (transcriptional regulator receptors)

View this table: [in this window] [in a new window]   TABLE 7 Family codesa

View this table: [in this window] [in a new window]   TABLE 8 Receptor type codes The use of an alphanumeric abbreviation for the receptor type category would allow either for recognizable reference to trivial names or direct reference for more recently identified receptors to the simple numbering system used by molecular biologists. Parenthetically, it is suggested that in some cases, for example the muscarinic acetylcholine and dopamine receptor families, consideration should be given as to whether the latter current schemes are still appropriate (see Humphrey, 1997). Regardless, the two options for designating an RC are outlined below and each subcommittee could choose one for their receptor family.

An RC will be reserved for the polypeptide product(s) of a single orthologous gene. Species variants will share a common RC but will be differentiated by a three-letter species code (see tables 9 and 10). A provisional RC can be assigned without cloning of the relevant gene providing it has been characterized robustly in whole tissues (e.g., histamine H₃ receptor). This may prove difficult in the brain, or in other tissues if multiple subtypes co-occur. Where this is so, the minimum requirement for a recombinant receptor to be accepted as a functional entity will be that robust operational (which must include transductional) data are provided for the heterologously expressed receptor and that its messenger ribonucleic acid, or the protein itself, is shown to occur in vivo. Recombinant receptors which have not been shown to be functional in whole tissues (e.g., 5-ht_5b) would be assigned only a provisional RC code number designated by a terminal upper case "P" (e.g., 2.1.5HT.05B.RNO.00.00.P).

View this table: [in this window] [in a new window]   TABLE 9 Species codesa

View this table: [in this window] [in a new window]   TABLE 10 Splice variant codesa

For structural classes in which hetero-oligomeric receptors occur, RCs for individual subunits often will be represented instead of the entire multimeric receptor, because the composition of the latter is usually indeterminate at present. Subunit RCs will be indicated by a terminal upper case "S" [e.g., 1.4.NUCT.01.00.00.S in the case of the P2X₁ receptor subunit for adenosine triphosphate (ATP)]. Where the subunit composition of an endogenous heteromeric receptor becomes known, that receptor is represented by a unique RC of its own (indicated by a terminal upper case "M" to represent a "multimeric" receptor); its subunit composition would be indicated in the database by listing the component RCs (S), and their stoichiometry when definitely known. For many transmitter-gated ion-channel receptors in Class 1, where a subunit combinatorial system occurs, the exact stoichiometry is not known currently. However, the situation is less complex for hetero-oligomers occurring in Class 3 where there is usually a fixed composition of subunits for each receptor type.

	IV. Conclusions

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We have provided justification for a systematic method of coding receptors of all structural types. The RC system proposed is designed not just to be informative but also to provide a distinct alphanumeric descriptor for each receptor protein. It is intended that each individual RC will not only define each receptor type unambiguously by way of a simple reference for publication purposes, but that it will also associate automatically with a large body of information in an authoritative pharmacological database. This database would supply an urgent need of pharmacologists and other scientists interested in the correlation and integration of data on receptor operation with that on receptor structure. The IUPHAR Receptor Database will link not only with existing databases already established for gene nucleotide sequences and amino acid sequences of receptor proteins, but will also uniquely provide detailed pharmacological data on the characteristics of receptor recognition and transduction. The latter data will be approved by international panels of experts in each of the many existing and future NC-IUPHAR subcommittees established for the different receptor families (see Vanhoutte et al., 1994).

	Acknowledgments

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We wish to acknowledge the members of NC-IUPHAR and the Technical Subcommittee for their contributions to the debate which led to the development of these ideas. The memberships of the committees are listed in footnote b, page 272. IUPHAR is grateful to UNESCO for financial support toward the work of the NC-IUPHAR.

	Footnotes

^a Address for Correspondence: P.P.A. Humphrey, Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QJ, England.

^b Composition of the IUPHAR Committee on Receptor Nomenclature and Drug Classification: E.A. Barnard, T.I. Bonner, W.C. Bowman, P.B. Bradley, B.N. Dhawan, C.T. Dollery, B.B. Fredholm, C.R. Ganellin, T.P. Godfraind, M. Hamon, T.K. Harden, P.P.A. Humphrey, S.Z. Langer, T. Masaki, R. Paoletti, R.R. Ruffolo, M. Spedding, U.G. Trendelenburg, P.M. Vanhoutte, S.P. Watson. Technical subcommittee (and corresponding members): E.A. Barnard, T.I. Bonner, D. Hoyer, P.P.A. Humphrey, P. Leff, J. Lomasney, N.P. Shankley, D.H. Jenkinson, S.P. Watson (and R.B. Barlow, J.W. Black, D.E. Clarke, D. Colquhoun, R.F. Furchgott, J.P. Green, T.P. Kenakin, R.J. Lefkowitz, D.R. Waud).

	Abbreviations

ATP, adenosine triphosphate; CFTR, cystic fibrosis transmembrane regulator; EAA, excitatory amino acid; EC, Enzyme Commission; FMRF, Phe-Met-Arg-Phe amide; JAK, Janus kinase; Kir, inward rectifier potassium channel; NC-IUPHAR, IUPHAR Committee on Receptor Nomenclature and Drug Classification; RC, receptor code; Trk, a tyrosine kinase subunit of neurotrophin receptors. The other abbreviations used are defined in table 7 .

	References

Top Previous

• Barnard EA (1997) Protein structures in receptor classification. Ann N Y Acad Sci  812: 14-28[Free Full Text].
• Baukrowvitz T, Hwang TC, Nairn AC and Gadsby DC (1994) C1^- channel gating to an ATP hydrolysis cycle. Neuron  12: 473-478[Medline].
• Black JW and Leff P (1983) Operational models of pharmacological agonism. Proc R Soc Lond B Biol Sci  220: 141-162[Medline].
• Clement JP, Kunjilwar K, Gonzalez G, Schwanstecher M, Panten U, Aguilar-Bryan L and Bryan J (1997) Association and stoichiometry of K_ATP channel subunits. Neuron  18: 827-838[Medline].
• Cockroft VB, Ostedgaard DJ, Barnard EA and Lunt GG (1990) Modelling of agonist binding to the ligand-gated ion channel superfamily of receptors. Proteins  8: 386-397[Medline].
• Coleman RA, Smith WL and Narumiya S (1994) International Union of Pharmacology classification of prostanoid receptors: Properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev  46: 205-229[Medline].
• Cully DF, Paress PS, Liu KK, Schaeffer JM and Arena JP (1996) Identification of a Drosophila melanogaster glutamate-gated chloride channel sensitive to the antiparasitic agent avermectin. J Biol Chem  271: 20187-20191[Abstract/Free Full Text].
• Cully DF, Vassilatis DK, Liu KK, Paress PS, Van der Ploeg LH, Schaeffer JM and Arena JP (1994) Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature (Lond.)  371: 707-711[Medline].
• Eglen RM, Jasper JR, Chang DJ and Martin GR (1997) The 5-HT₇ receptor: Orphan found. Trends Pharmacol Sci  18: 104-107[Medline].
• Fairman WA, Vandenberg RJ, Arriza JL, Kavanaugh MP and Amara SG (1995) An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature (Lond.)  375: 599-603[Medline].
• Galli A, Petersen CI, de Blaquiere M, Blakely RD and DeFelice LJ (1997) Drosophila serotonin transporters have voltage-dependent uptake coupled to a serotonin-gated ion channel. Neuroscience  17: 3401-3411[Abstract/Free Full Text].
• Glusman G, Clifton S, Roe B and Lancet D (1996) Sequence analysis in the olfactory receptor gene cluster on human chromosome 17: Recombinatorial events affecting receptor diversity. Genomics  37: 147-160[Medline].
• Gribble FM, Tucker SJ and Ashcroft FM (1997) The essential role of the Walker A motifs of SUR1 in K-ATP activation of Mg-ADP and diazoxide. EMBO J  16: 1145-1152[Medline].
• Hoyer D, Bell GI, Berelowitz M, Epelbaum J, Feniuk W, Humphrey PPA, O'Carroll A-M, Patel YC, Schonbrunn A, Taylor JE and Reisine T (1995) Classification and nomenclature of somatostatin receptors. Trends Pharmacol Sci  16: 86-88[Medline].
• Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR and Humphrey PPA (1994) International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev  46: 157-203[Abstract].
• Humphrey PPA (1997) The characterization and classification of neurotransmitter receptors. Ann N Y Acad Sci  812: 1-13[Free Full Text].
• Humphrey PPA (1998) The characterization and classification of receptors, in Receptor-Based Drug Design (Leff P ed) pp 7-24, Marcel Dekker Inc, New York.
• Humphrey PPA, Hartig P and Hoyer D (1993) A proposed new nomenclature for 5-HT receptors. Trends Pharmacol Sci  14: 233-236[Medline].
• Humphrey PPA, Spedding M and Vanhoutte PM (1994) Receptor classification and nomenclature: The revolution and the resolution. Trends Pharmacol Sci  15: 203-204[Medline].
• Inagaki N, Gonoi T, Clement JP, Wang CZ, Aguilar-Bryan L, Bryan J and Seino S (1996) A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K⁺ channels. Neuron  16: 1011-1017[Medline].
• Ishihara H, Connolly AJ, Zeng D, Kahn ML, Zheng YW, Timmons C, Tram T and Coughlin SR (1997) Protease-activated receptor 3 is a second thrombin receptor in humans. Nature (Lond.)  386: 502-506[Medline].
• Jenkinson DH, Barnard EA, Hoyer D, Humphrey PPA, Leff P and Shankley NP (1995) International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification: IXRecommendations on terms and symbols in quantitative pharmacology. Pharmacol Rev  47: 255-266[Medline].
• Jing S, Wen D, Yu Y, Holst PL, Luo Y, Fang M, Tamir R, Antonio L, Hu Z, Cupples R, Louis JC, Hu S, Altrock BW and Fox GM (1996) GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-, a novel receptor for GDNF. Cell  85: 1113-1124[Medline].
• Karlin A and Akabas MH (1995) Toward a structural basis for the function of nicotinic acetylcholine receptors and their cousins. Neuron  15: 1231-1244[Medline].
• Kastner P, Mark M and Chambon P (1995) Nonsteroid nuclear receptors: What are genetic studies telling us about their role in real life? Cell  83: 859-869[Medline].
• Kenakin TP, Bond RA and Bonner TI (1992) Definition of pharmacological receptors. Pharmacol Rev  44: 351-362[Medline].
• Klein RD, Sherman D, Ho WH, Stone D, Bennett GL, Moffat B, Vandlen R, Simmons L, Gu Q, Hongo JA, Devaux B, Poulsen K, Armanini M, Nozaki C, Asai N, Goddard A, Phillips H, Henderson CE, Takahashi M and Rosenthal A (1997) A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor. Nature (Lond.)  387: 717-721[Medline].
• Kolakowski LF (1994) GCRDb: A G-protein-coupled receptor database. Receptors Channels  2: 1-7[Medline].
• Laudet V, et al. (1998) A unified nomenclature system for the nuclear receptors superfamily. Paper discussed at: NC-IUPHAR meeting; January 17-18, 1998, Saint Jean Cap Ferrat, France.
• Lesage F, Guillemare E, Fink M, Duprat F, Heurteaux C, Fosset M, Romey G, Barhanin J and Lazdunski M (1995) Molecular properties of neuronal G-protein-activated inwardly rectifying K⁺ channels. J Biol Chem  270: 28660-28667[Abstract/Free Full Text].
• Lingueglia E, Champigny G, Lazdunski M and Barbry P (1995) Cloning of the amiloride-sensitive FMRF amide peptide-gated sodium channel. Nature (Lond.)  378: 730-733[Medline].
• Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P and Evans RM (1995) The nuclear receptor superfamily: The second decade. Cell  83: 835-839[Medline].
• Misrahi M, Ghinea N, Sar S, Saunier B, Jolivet A, Loosfelt H, Cerutti M, Devauchelle G and Milgrom E (1994) Processing of the precursors of the human thyroid-stimulating hormone receptor in various eukaryotic cells (human thyrocytes, transfected L cells and baculovirus-infected insect cells). Eur J Biochem  222: 711-719[Medline].
• Narumiya S (1996) Prostanoid receptors and signal transduction. Prog Brain Res  113: 231-241[Medline].
• Nistri A and Arenson MS (1983) Multiple postsynaptic responses evoked by glutamate on in vitro spinal motoneurons. Adv Biochem Psychopharmacol  37: 229-236[Medline].
• North RA and Barnard EA (1997) Nucleotide receptors. Curr Opin Neurobiol  7: 346-357[Medline].
• Nystedt S, Larsson AK, Åberg H and Sundelin J (1995) The mouse proteinase-activated receptor-2 cDNA and gene: Molecular cloning and functional expression. J Biol Chem  270: 5950-5955[Abstract/Free Full Text].
• Picaud SA, Larsson HP, Grant GB, Lecar H and Werblin FS (1995) Glutamate-gated chloride channel with glutamate-transporter-like properties in core photoreceptors of the tiger salamander. J Neurophysiol  74: 1760-1771[Abstract/Free Full Text].
• Sachais BS, Snider RM, Lowe JA III and Krause JE (1993) Molecular basis for the species selectivity of the substance P antagonist CP-96,345. J Biol Chem  268: 2319-2323[Abstract/Free Full Text].
• Schindler M, Humphrey PPA and Emson PC (1996) Somatostatin receptors in the central nervous system. Prog Neurobiol  50: 9-47[Medline].
• Sonders MS and Amara SG (1996) Channels in transporters. Curr Opin Neurobiol  6: 294-302[Medline].
• Sonders MS, Zhu SJ, Zahniser NR, Kavanaugh MP and Amara SG (1997) Multiple ionic conductances of the human dopamine transporter: The actions of dopamine and psychostimulants. J Neurosci  17: 960-974[Abstract/Free Full Text].
• Takumi T, Ishii T, Horio Y, Morishige K-I, Takahashi N, Yamada M, Yamashita T, Kiyama H, Sohmiya K, Nakanishi S and Kurachi Y (1995) A novel ATP-dependent inward rectifier potassium channel expressed predominantly in glial cells. J Biol Chem  270: 16339-16346[Abstract/Free Full Text].
• Tucker SJ, Gribble FM, Zhao C, Trapp S and Ashcroft FM (1997) Truncation of Kir6.2 produces ATP-sensitive K⁺ channels in the absence of the sulfonylurea receptor. Nature (Lond.)  387: 179-183[Medline].
• Vanetti M, Vogt G and Hollt V (1993) The two isoforms of the mouse somatostatin receptor (mSSTR2A and mSSTR2B) differ in coupling efficiency to adenylate cyclase and in agonist-induced receptor desensitization. FEBS Lett  331: 260-266[Medline].
• Vanhoutte PM, Barnard EA, Cosmides GJ, Humphrey PPA, Spedding M and Godfraind T (1994) International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. Pharmacol Rev  46: 111-116[Medline].
• Vanhoutte PM, Humphrey PPA and Spedding M (1996) X: International Union of Pharmacology recommendations for nomenclature of new receptor subtypes. Pharmacol Rev  48: 1-2[Medline].
• Vu TK, Hung DT, Wheaton VI and Coughlin SR (1991) Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell  64: 1057-1068[Medline].
• Waldmann R, Champigny G, Bassilana F, Heurteaux C and Lazdunski M (1997) A proton-gated cation channel involved in acid-sensing. Nature (Lond.)  386: 173-177[Medline].

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