Muscarinic Cholinergic Receptors in Human Foetal Brain: Characterization and Ontogeny of [³H]Quinuclidinyl Benzilate Binding Sites in Frontal Cortex

Abstract

Twenty-two frontal cortices from normal human foetal brains of gestational ages ranging from 16 to 40 weeks and five postnatal brains ranging from 5 to 50 years were analysed for the ontogeny of muscarinic receptors using [3H]quinuclidinyl benzilate (QNB) as the ligand. QNB binding sites were shown to be stable up to 4 1/2 months of storage at -70 degrees C. QNB binding was characterized in frontal cortices of 28-week-old foetal brains as muscarinic receptors by the following criteria: (1) it was localised mainly in particulate fraction; (2) binding was saturable at a concentration of 1.5 nM; (3) the cholinergic antagonists atropine and scopolamine competed for the binding, with IC50 values of 1 and 0.8 nM, respectively. The agonists oxotremorine, carbachol, and pilocarpine gave IC50 values of 1, 15 and 18 microM, respectively. Nicotinic receptor ligands and noncholinergic drugs could not compete for the binding. Bimolecular association and dissociation rate constants for the reversible binding are 6.23 X 10(8) M-1 X min-1 and 2.0 X 10(-2) X min-1, respectively. The equilibrium dissociation constant is 33 pM. The KD obtained by saturation binding data is 103 pM. Ontogeny of muscarinic receptors showed three distinct phases: In phase I, they appear between 16 and 18 weeks [average concentration 109 fmol/mg protein of total particulate fraction (TPF)] and slowly increase up to 20 weeks (average concentration 147 fmol/mg protein TPF). Phase II is a lag period between 20 and 24 weeks at which time receptor concentration does not change perceptibly (average concentration (67 fmol/mg protein TPF).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term effects of methamphetamine exposure on cognitive function and muscarinic acetylcholine receptor levels in mice

“…In the mouse brain, mAChRs increase during the first three postnatal weeks of life (Aubert et al , 1996), the same period during which the hippocampus develops (Bayer et al , 1982; Altman and Bayer 1990; Clancy et al , 2001., 2007a). Consistent with these mouse data, there is an increase in mAChRs and hippocampal development in the human fetal brain during the third trimester (Ravikumar and Sastry 1985; Rice and Barone 2000). In children, in utero MA exposure results in smaller hippocampal volumes (Chang et al , 2004).…”

Synchronized overproduction of neurotransmitter receptors in diverse regions of the primate cerebral cortex.

“…An excess of neurotransmitter receptors followed by elimination has been reported for selected cortical areas in rodents and cats (27)(28)(29)(30)(31)(32)(33)(34), but synchronous overproduction of several neurotransmitter receptors in anatomically and functionally diverse areas of the neocortex is unexpected. We attribute the observed changes in the density of neurotransmitter receptors to an initial overproduction followed by a decrease of binding sites during infancy and adolescence.…”

Postnatal development of the human primary motor cortex: a quantitative cytoarchitectonic analysis

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