Identification of critical IgG binding epitopes on the neonatal Fc receptor.

The neonatal Fc receptor (FcRn) binds maternal immunoglobulin G (IgG) during the acquisition of passive immunity by the fetus or newborn. FcRn also binds IgG and returns it to the bloodstream, thus protecting IgG from a default degradative pathway. Biosensor assays have been used to characterize the interaction of a soluble form of rat FcRn with IgG, and demonstrate that FcRn dimerization and immobilization are necessary to reproduce in vivo binding characteristics. Here, we report the identification of several FcRn amino acid substitutions that disrupt its affinity for IgG and examine the effect of alteration of residues at the FcRn dimer interface. The role of these amino acids is discussed in the context of the previously reported structures of rat FcRn and a complex of FcRn with the Fc portion of IgG.

Postnatal development of cholinergic presynaptic inhibition in rat hippocampus.

Muscarinic depression of field potential excitatory postsynaptic potentials (fEPSPs) in striatum radiatum of area CA1 was compared in hippocampal slices from rats of different ages. Bath application of 4 microM muscarine reversibly depressed the fEPSP slope by 68.4% in slices from adult animals (P43-P60), but caused only a 32.2% depression in slices from P5-P7 animals. The magnitude of the depression increased with age during the first postnatal month. Reduced sensitivity of excitatory synaptic transmission to cholinergic depression during postnatal development could be one factor contributing to the hyperexcitability of immature hippocampus.

Characterization of [3H]quipazine binding to 5-hydroxytryptamine3 receptors in rat brain membranes.

[3H]Quipazine was used to label binding sites in rat brain membranes that display characteristics of a 5-hydroxytryptamine3 (5-HT3) receptor. The radioligand binds with high affinity (KD, 1.2 +/- 0.1 nM) to a saturable population of sites (Bmax, 3.0 +/- 0.4 pmol/g of tissue) that are differentially located in the brain. Specific [3H]quipazine binding is not affected by guanine or adenine nucleotides. ICS 205-930, BRL 43964, Lilly 278584, and zacopride display less than nanomolar affinity for these sites whereas MDL 72222 is approximately one order of magnitude less potent. The pharmacological profile of the binding site is in excellent agreement with that of 5-HT3 receptors characterized in peripheral physiological models. We conclude that [3H]quipazine labels a 5-HT3 receptor in the rat CNS.