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Distribution of Three Nicotinic Receptor α4 mRNA Transcripts in Rat Brain: Selective Regulation by Nicotine Administration


Address correspondence and reprint requests to Dr. L. Wecker at Department of Pharmacology and Therapeutics, USF College of Medicine, MDC Box 9, 12901 Bruce B. Downs Blvd., Tampa, FL 33612-4799, U.S.A.


Abstract: Northern blot analysis determined whether multiple α4 transcripts for neuronal nicotinic receptors in rat brain could be detected as distinct bands. When poly(A)+ RNA was isolated from brain regions and hybridized with a Hinfl fragment of α4-1 cDNA containing a sequence shared by both α4-1 and α4-2, but little homology with other α or β subunits, bands at 6.0, 4.6, and 2.6 kb were obtained. When a Taql fragment with selectivity for α4-1 was used, a single band was present at 6.0 kb. The 6.0-kb band was least abundant in all brain regions; the 2.6-kb band was most abundant in frontal cortex, hippocampus, striatum, basal forebrain, and thalamus, whereas the 4.6-kb band was most abundant in midbrain and cerebellum. Nicotine (3.6 µmol/kg, s.c., twice daily) increased the abundance of the 4.6-kb transcript in frontal cortex significantly by 28% following 2.5 days of injections; the 6.0- and 2.6-kb transcripts were unchanged. Nicotine did not affect α4 transcripts in other brain regions. Results suggest that increased mRNA levels may mediate the nicotine-induced up-regulation of receptors in cerebral cortex.