Functional Expression of a New Pharmacological Subtype of Brain Nicotinic Acetylcholine Receptor

• Published in: Science (American Association for the Advancement of Science) Vol. 240; no. 4850; pp. 330 - 334
• Main Authors: Wada, Keiji, Ballivet, Marc, Boulter, Jim, Connolly, John, Wada, Etsuko, Deneris, Evan S., Swanson, Larry W., Heinemann, Steve, Patrick, Jim
• Format: Journal Article
• Language: English
• Published: Washington, DC The American Association for the Advancement of Science 15.04.1988; American Association for the Advancement of Science
• Subjects: acetylcholine; Amino Acid Sequence; Amino acid sequencing; Amino acids; Analysis; Animals; Base Sequence; Biochemistry; Biological and medical sciences; Brain; Brain - metabolism; Cell lines; Cell receptors; Cell structures and functions; Complementary DNA; DNA; DNA Restriction Enzymes; Exons; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Generally accepted auditing standards; Genes; Genetics; Genomics; Medical research; Messenger RNA; Molecular and cellular biology; Molecular Sequence Data; Neurons - metabolism; Neurotransmitter receptors; Nucleotide Mapping; Oocytes; Oocytes - metabolism; Protein research; Rats; Receptors; Receptors, Nicotinic - genetics; Receptors, Nicotinic - metabolism; Transcription, Genetic; Xenopus laevis; Brain; Molecular hybridization; In vitro translation; Rat; In situ; Rodentia; Central nervous system; Gene expression; Vertebrata; Cholinergic receptor; Mammalia; Microinjection; Molecular cloning; Nicotinic receptor; Aminoacid sequence
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2832952

A new type of agonist-binding subunit of rat neuronal nicotinic acetylcholine receptors (nAChRs) was identified. Rat genomic DNA and complementary DNA encoding this subunit (alpha2) were cloned and analyzed. Complementary DNA expression studies in Xenopus oocytes revealed that the injection of messenger RNAs (mRNAs) for alpha2 and beta2 (a neuronal nAChR subunit) led to the generation of a functional nAChR. In contrast to the other known neuronal nAChRs, the receptor produced by the injection of alpha2 and beta2 mRNAs was resistant to the α-neurotoxin Bgt3.1. In situ hybridization histochemistry showed that alpha2 mRNA was expressed in a small number of regions, in contrast to the wide distribution of the other known agonist-binding subunits (alpha3 and alpha4) mRNAs. These results demonstrate that the alpha2 subunit differs from other known agonist-binding α-subunits of nAChRs in its distribution in the brain and in its pharmacology.