Biomaterial Database

[3H](-)nicotine binding sites in fetal human brain. 1988

N J Cairns, and S Wonnacott

Department of Biochemistry, University of Bath, U.K.

The development of putative nicotinic binding sites in brains from human fetuses of 12-19 weeks gestation was studied. The binding of [3H](-)nicotine to fetal human brain membranes, using a rapid filtration method, was saturable and stereospecific. Scatchard analysis revealed a single class of high affinity sites with a Kd of 1.5 +/- 0.5 nM and a Bmax of 4.5 +/- 1.9 fmol/mg protein (n = 11). [3H](-)nicotine binding increased between the ages of 12 and 19 weeks in human fetal brain (r = 0.63, n = 20, P less than 0.01). In competition studies nicotinic agonists were the most effective in inhibiting [3H](-)nicotine binding whereas antagonists were relatively ineffective. Ki values for displacing ligands in the presence of [3H](-)nicotine were: cytisine, 1.6 nM; (-)nicotine, 16 nM; (+) nicotine, 510 nM; dihydro-beta-erythroidine, 1.9 microM; dimethyl-4-phenylpiperazinium, 6.5 microM; choline chloride, 25 microM. Atropine and alpha-bungarotoxin failed to inhibit binding up to 50 microM. Comparison of dissected brain regions revealed regional variations in the density of nicotinic binding sites: specific binding of [3H](-)nicotine was greatest in the nucleus basalis of Meynert, globus pallidus, caudate-putamen and thalamus, and lowest in the medulla. These results are interpreted in relation to the development of functional cholinergic transmission in human fetal brain, and the potential vulnerability of this system to maternal tobacco usage.

UI	MeSH Term	Description	Entries
D009538	Nicotine	Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.	Nicotine Bitartrate,Nicotine Tartrate
D011807	Quinolizines
D011978	Receptors, Nicotinic	One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.	Nicotinic Acetylcholine Receptors,Nicotinic Receptors,Nicotinic Acetylcholine Receptor,Nicotinic Receptor,Acetylcholine Receptor, Nicotinic,Acetylcholine Receptors, Nicotinic,Receptor, Nicotinic,Receptor, Nicotinic Acetylcholine,Receptors, Nicotinic Acetylcholine
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D005314	Embryonic and Fetal Development	Morphological and physiological development of EMBRYOS or FETUSES.	Embryo and Fetal Development,Prenatal Programming,Programming, Prenatal
D005865	Gestational Age	The age of the conceptus, beginning from the time of FERTILIZATION. In clinical obstetrics, the gestational age is often estimated from the onset of the last MENSTRUATION which is about 2 weeks before OVULATION and fertilization. It is also estimated to begin from fertilization, estrus, coitus, or artificial insemination.	Embryologic Age,Fetal Maturity, Chronologic,Chronologic Fetal Maturity,Fetal Age,Maturity, Chronologic Fetal,Age, Embryologic,Age, Fetal,Age, Gestational,Ages, Embryologic,Ages, Fetal,Ages, Gestational,Embryologic Ages,Fetal Ages,Gestational Ages
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000470	Alkaloids	Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)	Alkaloid,Plant Alkaloid,Plant Alkaloids,Alkaloid, Plant,Alkaloids, Plant
D001392	Azocines
D001667	Binding, Competitive	The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.	Competitive Binding