Distribution of three nicotinic receptor alpha 4 mRNA transcripts in rat brain: selective regulation by nicotine administration.
Northern blot analysis determined whether multiple alpha 4 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 alpha 4-1 cDNA containing a sequence shared by both alpha 4-1 and alpha 4-2, but little homology with other alpha or beta subunits, bands at 6.0, 4.6, and 2.6 kb were obtained. When a Taql fragment with selectivity for alpha 4-1 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 mumol/kg, a.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 alpha 4 transcripts in other brain regions. Results suggest that increased mRNA levels may mediate the nicotine-induced up-regulation of receptors in cerebral cortex.
Yu
Z J
ZJ
Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, Tampa 33612-4799, USA.
Morgan
D G
DG
Wecker
L
L
D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism*; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000235:genetics*; D014018:Tissue Distribution
D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D009538:Nicotine