α9α10 nicotinic acetylcholine receptors regulate murine bone marrow granulocyte functions.

Polymorphonuclear neutrophilic granulocytes (PMNs) are extremely important in defense of the organism against infections and in inflammatory processes including neuroinflammation and pain sensation. Different subtypes of nicotinic acetylcholine receptors (nAChRs) are involved in modulation of PMN activities. Earlier we determined expression of α2-7, α9, β3, β4 subunits and regulatory role of α7 and α3β2 nAChR subtypes in functions of inflammatory PMNs.

Snake C-type lectin-like proteins inhibit nicotinic acetylcholine receptors.

Venoms of viperid snakes affect mostly hemostasis, while C-type lectin-like proteins (CTLPs), one of the main components of viperid venoms, act as anticoagulants, procoagulants, or agonists/antagonists of platelet activation. However, we have shown earlier that CTLPs from the saw-scaled viper , called emunarecins EM1 and EM2, were able to inhibit nicotinic acetylcholine receptors (nAChRs) in neurons of a pond snail (). Here we analysed the structure of the emunarecins by mass spectrometry and report that EM1 and EM2 inhibit fluorescent α-bungarotoxin binding to both muscle-type nAChRs from and human neuronal α7 nAChRs.

PNU-120596, a positive allosteric modulator of mammalian α7 nicotinic acetylcholine receptor, is a negative modulator of ligand-gated chloride-selective channels of the gastropod Lymnaea stagnalis.

Excitatory α7 neuronal nicotinic receptors (nAChR) are widely expressed in the central and peripheral nervous and immune systems and are important for learning, memory, and immune response regulation. Specific α7 nAChR ligands, including positive allosteric modulators are promising to treat cognitive disorders, inflammatory processes, and pain. One of them, PNU-120596, highly increased the neuron response to α7 agonists and retarded desensitization, showing selectivity for α7 as compared to heteromeric nAChRs, but was not examined at the inhibitory ligand-gated channels.

Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors.

Phospholipases A2 (PLA2s) are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in the sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes. PLA2s from snake venoms have numerous toxic effects, not all of which can be explained by phospholipid hydrolysis, and each enzyme has a specific effect.

Peptides from puff adder Bitis arietans venom, novel inhibitors of nicotinic acetylcholine receptors.

Phospholipase A (named bitanarin) possessing capability to block nicotinic acetylcholine receptors (nAChRs) was isolated earlier (Vulfius et al., 2011) from puff adder Bitis arietans venom. Further studies indicated that low molecular weight fractions of puff adder venom inhibit nAChRs as well.

Nicotinic receptor involvement in regulation of functions of mouse neutrophils from inflammatory site.

Participation of nicotinic acetylcholine receptors (nAChRs) in functioning of polymorphonuclear neutrophils (PMNs) isolated from inflammatory site of mice and expression of different nAChR subunits were studied. Nicotine and acetylcholine (ACh) modified respiratory burst induced by a chemotactic peptide N-formyl-MLF in neutrophils of male (but not female) mice. Antagonists of nAChRs α-cobratoxin (αCTX), α-conotoxins MII and [A10L]PnIA at concentrations of 0.

Inhibition of nicotinic acetylcholine receptors, a novel facet in the pleiotropic activities of snake venom phospholipases A2.

Phospholipases A2 represent the most abundant family of snake venom proteins. They manifest an array of biological activities, which is constantly expanding. We have recently shown that a protein bitanarin, isolated from the venom of the puff adder Bitis arietans and possessing high phospholipolytic activity, interacts with different types of nicotinic acetylcholine receptors and with the acetylcholine-binding protein.

An unusual phospholipase A₂ from puff adder Bitis arietans venom--a novel blocker of nicotinic acetylcholine receptors.

The venoms of snakes from Viperidae family mainly influence the function of various blood components. However, the published data indicate that these venoms contain also neuroactive components, the most studied being neurotoxic phospholipases A₂ (PLA₂s). Earlier we have shown (Gorbacheva et al.

Alpha-conotoxin analogs with enhanced affinity for nicotinic receptors and acetylcholine-binding proteins.

Alpha-conotoxins, neurotoxic peptides from poisonous Conus marine snails, can be subdivided into several groups targeting distinct subtypes of nicotinic acetylcholine receptors (nAChRs). Such alpha-conotoxins as, for example, GI, MI, or SIA potently block muscle-type nAChRs from muscles and from the electric organ of Torpedo ray, whereas others target distinct neuronal nAChRs: alpha-conotoxins ImI and PnIB block pentaoligomeric alpha7 nAChRs, and alpha-conotoxins MII or PnIA inhibit heteromeric nAChRs made of combinations of alpha3 or alpha6 subunits with beta2 subunit. alpha-Conotoxins interact with N-terminal extracellular ligand-binding domains of nAChRs and are indispensable tools for distinguishing various subtypes of AChRs at normal and pathological states.

Alpha-conotoxin analogs with additional positive charge show increased selectivity towards Torpedo californica and some neuronal subtypes of nicotinic acetylcholine receptors.

Alpha-conotoxins from Conus snails are indispensable tools for distinguishing various subtypes of nicotinic acetylcholine receptors (nAChRs), and synthesis of alpha-conotoxin analogs may yield novel antagonists of higher potency and selectivity. We incorporated additional positive charges into alpha-conotoxins and analyzed their binding to nAChRs. Introduction of Arg or Lys residues instead of Ser12 in alpha-conotoxins GI and SI, or D12K substitution in alpha-conotoxin SIA increased the affinity for both the high- and low-affinity sites in membrane-bound Torpedo californica nAChR.