Ontogenesis of nicotinic acetylcholine receptors and presynaptic cholinergic neurons in mammalian brain.
We find a significantly lower level of specific [3H]nicotine binding in the fetal rat forebrain of 20 day gestational age as compared to adult rat tissue, and a progressive increase in the [3H]nicotine binding in the early neonatal forebrain, reaching adult level at 14-28 days of age. The maximal binding sites (Bmax) for the brain [3H]-nicotine binding at the ages of 3, 14 and 28 days were 36%, 74% and 98% respectively of the adult value. Neosurugatoxin (NSTX) was a potent inhibitor of [3H]nicotine binding in the neonatal forebrain (IC50 = 205, 81 and 103 nM at the 3, 14 and 28 days of age) as well as in the adult tissue (IC50 = 79 nM). Both the choline acetyltransferase (ChAT) activity and high affinity uptake of [14C]choline were not detectable or extremely low in the 1 week neonatal forebrain, and then increased progressively with age to reach the adult level at about 6 weeks of age. These data indicate that central nicotinic receptors may mature prior to the development of presynaptic cholinergic elements.
D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development*; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000166:cytology*; D005260:Female; D007700:Kinetics; D008978:Mollusk Venoms / Q000494:pharmacology; D009474:Neurons / Q000032:analysis*; D009538:Nicotine / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011950:Receptors, Cholinergic / Q000032:analysis*
D008978:Mollusk Venoms; D011950:Receptors, Cholinergic; D009538:Nicotine; C036793:neosurugatoxin; D002795:Choline O-Acetyltransferase; D002794:Choline