The heteromeric 5-HT3A/B receptor:the effect of 5-HT3B subunits on receptor structure and ligand recognition

The 5-HT3 receptors are members of the cys-loop family of ligand-gated ion channels. Two functional subtypes are known, the homomeric 5HT3A and the heteromeric 5HT3A/B receptors, which exhibit distinct biophysical characteristics but are difficult to differentiate pharmacologically. Atomic force microscopy has been used to determine the stoichiometry and architecture of the heteromeric 5HT3A/B receptor. Each subunit was engineered to express a unique C-terminal epitope tag, together with six sequential histidine residues to facilitate nickel affinity purification. The 5-HT3 receptors, ectopically expressed in HEK293 cells, were solubilised, purified and decorated with antibodies to the subunit specific epitope tags. Imaging of individual receptors by atomic force microscopy revealed a pentameric arrangement of subunits in the order BBABA, reading anti-clockwise when viewed from the extracellular face. Homology models for the heteromeric receptor were then constructed using both the electron microscopic structure of the nicotinic acetylcholine receptor, from Torpedo marmorata, and the X-ray crystallographic structure of the soluble acetylcholine binding protein, from Lymnaea stagnalis, as templates. These homology models were used, together with equivalent models constructed for the homomeric receptor, to interpret mutagenesis experiments designed to explore the minimal recognition differences of both the natural agonist, 5-HT, and the competitive antagonist, granisetron, for the two human receptor subtypes. The results of this work revealed that the 5-HT3B subunit residues within the ligand binding site, for both the agonist and antagonist, are accommodating to conservative mutations. They are consistent with the view that the 5-HT3A subunit provides the principal and the 5-HT38 subunit the complementary recognition interactions at the binding interface.

Study and comparison on freshwater snail fauna in the paddy fields and related river and lake (Babolroad & Parishan) water supply in Mazandaran & Frace provinces of Iran

As a result of this investigation, for the first time from Babolroud river in Iran is 15 species identified, which they belong to 8 genera, from 7 families. The most and least distribution, 13 and 5 species, belong to Miandasht and Rostaye Anarestane Babol stations respectively, which they are 50 kilometers away from each other. Also 20 species belong to 10 genera from 6 families were identified in Parishan lake. The most the distribution belong to stations 1 and 5 with 6 and 18 species respectively. The most commonly distributed family is Lymnaeidae with 6 species: Lyamnaea truncatula, L. auricularia, L. palustris, L. pereger, L. stagnalis and L. gedrosiana, which L. trancatula is identified as the most frequent and has medical importance. L. stagnalis is identified to be the most important to agriculture. Planorbis planorhis, Physa acuta, Lymnaea pereger, Bithynia tenculata and Vavata piscinalis are reported for the first time from this region.