Identification and characterization of three new alternatively spliced μ-opioid receptor isoforms

被引：177

作者：

Pan, YX ^{[1
]}

Xu, J ^{[1
]}

Bolan, E ^{[1
]}

Abbadie, C ^{[1
]}

Chang, A ^{[1
]}

Zuckerman, A ^{[1
]}

Rossi, G ^{[1
]}

Pasternak, GW ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Neurol, Cotzias Lab Neurooncol, New York, NY 10021 USA

来源：

MOLECULAR PHARMACOLOGY | 1999年 / 56卷 / 02期

关键词：

D O I：

10.1124/mol.56.2.396

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

We have identified four new mu-opioid receptor (MOR)-1 exons, indicating that the gene now contains at least nine exons spanning more than 200 kilobases. Replacement of exon 4 by combinations of the new exons yields three new receptors. When expressed in Chinese hamster ovary cells, all three variants displayed high affinity for mu-opioid ligands, but kappa and delta drugs were inactive. However, there were subtle, but significant, differences in the binding profiles of the three variants among themselves and from MOR-1. Immunohistochemically, the major variant, MOR-1C, displayed a regional distribution quite distinct from that of MOR-1. Region-specific processing also was seen at the mRNA level. Antisense mapping revealed that the four new exons were all involved in morphine analgesia. Together with two other variants generated from alternative splicing of exon 4, there are now six distinct MOR-1 receptors.

引用

页码：396 / 403

页数：8

共 48 条

[21] μ opioid receptor knockout in mice:: effects on ligand-induced analgesia and morphine lethality [J].

Loh, HH ;

Liu, HC ;

Cavalli, A ;

Yang, WL ;

Chen, YF ;

Wei, LN .

MOLECULAR BRAIN RESEARCH, 1998, 54 (02) :321-326

[22]

LOWRY OH, 1951, J BIOL CHEM, V193, P265

[23] NEW PLAYERS IN THE 5-HT RECEPTOR FIELD - GENES AND KNOCKOUTS [J].

LUCAS, JJ ;

HEN, R .

TRENDS IN PHARMACOLOGICAL SCIENCES, 1995, 16 (07) :246-252

[24] Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene [J].

Matthes, HWD ;

Maldonado, R ;

Simonin, F ;

Valverde, O ;

Slowe, S ;

Kitchen, I ;

Befort, K ;

Dierich, A ;

LeMeur, M ;

Dolle, P ;

Tzavara, E ;

Hanoune, J ;

Roques, BP ;

Kieffer, BL .

NATURE, 1996, 383 (6603) :819-823

[25] GENOMIC STRUCTURE AND ANALYSIS OF PROMOTER SEQUENCE OF A MOUSE MU-OPIOID RECEPTOR GENE [J].

MIN, BH ;

AUGUSTIN, LB ;

FELSHEIM, RF ;

FUCHS, JA ;

LOH, HH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (19) :9081-9085

[26] ALTERNATIVE SPLICING OF C-TERMINAL TAIL OF PROSTAGLANDIN-E RECEPTOR SUBTYPE-EP3 DETERMINES G-PROTEIN SPECIFICITY [J].

NAMBA, T ;

SUGIMOTO, Y ;

NEGISHI, M ;

IRIE, A ;

USHIKUBI, F ;

KAKIZUKA, A ;

ITO, S ;

ICHIKAWA, A ;

NARUMIYA, S .

NATURE, 1993, 365 (6442) :166-170

[27] CLONING, EXPRESSION AND CLASSIFICATION OF A KAPPA(3)-RELATED OPIOID RECEPTOR USING ANTISENSE OLIGODEOXYNUCLEOTIDES [J].

PAN, YX ;

CHENG, J ;

XU, J ;

PASTERNAK, GW .

REGULATORY PEPTIDES, 1994, 54 (01) :217-218

[28]

Pan YX, 1996, FEBS LETT, V395, P207

[29] MAPPING OF OPIOID RECEPTORS USING ANTISENSE OLIGODEOXYNUCLEOTIDES - CORRELATING THEIR MOLECULAR-BIOLOGY AND PHARMACOLOGY [J].

PASTERNAK, GW ;

STANDIFER, KM .

TRENDS IN PHARMACOLOGICAL SCIENCES, 1995, 16 (10) :344-350

[30] PHARMACOLOGICAL MECHANISMS OF OPIOID ANALGESICS [J].

PASTERNAK, GW .

CLINICAL NEUROPHARMACOLOGY, 1993, 16 (01) :1-18

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