| Autor: |
K M, Garrett, N, Saito, R S, Duman, M S, Abel, R A, Ashton, S, Fujimori, B, Beer, J F, Tallman, M P, Vitek, A J, Blume |
| Rok vydání: |
1990 |
| Předmět: |
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| Zdroj: |
Molecular pharmacology. 37(5) |
| ISSN: |
0026-895X |
| Popis: |
A 1.8-kilobase (kb) cDNA clone for a beta 1 subunit of the human gamma-aminobutyric acidA (GABAA) receptor has been isolated and sequenced. The longest open reading frame of the clone, pCLL610, contains nucleotide sequence encoding a portion of the putative signal sequence followed by 449 amino acids of the entire mature protein. The deduced amino acid sequence of pCLL610 differs from a recently described human beta 1 subunit by a single amino acid. The amino acid sequences of the human GABAA receptor beta 1 subunits share 98% identity with the beta 1 subunits of the bovine and rat GABAA receptor, with the majority of the differences occurring in the intracellular loop between the M3 and M4 transmembrane regions of the protein. A single 11-kb transcript is observed in Northern blots of poly(A)+ RNA isolated from rat brain probed with nick-translated pCLL610. In human brain, the pCLL610 probe recognized the 11-kb message, in addition to two other bands between 8 and 11-kb. Developmental studies of rat brain mRNA show that the message of the GABAA beta 1 subunit is highest at birth, rapidly decreases, and reaches adult levels of 5 to 7 days of age. This is in contrast to the development of the alpha 1 subunit, which is low from days 1 to 5 and increases to adult levels by days 14 to 25. Relative levels of the mRNA for the alpha 1 and beta 1 subunits vary among rat brain regions. The levels of mRNA for the alpha 1 subunit are similar in the cortex, hippocampus, and midbrain, whereas cerebellar levels are twice those in the cortex. The rank order of the relative amount of beta 1 subunit message is hippocampus greater than cortex = midbrain greater than cerebellum. These data, taken with our previous study of the alpha 1 subunits of the GABAA receptor, suggest that the differences in the distribution and regulation of the alpha 1 and beta 1 subunits may reflect a variety of subunit combinations forming the GABAA receptor. Heterogeneity in the GABAA receptor composition may provide a molecular basis for the diverse pharmacological properties associated with this receptor. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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