Itch in Hymenoptera Sting Reactions

Insect stings and the resulting itch are a ubiquitous problem. Stings by members of the insect order Hymenoptera, which includes sawflies, wasps, bees and ants, and especially by bees and wasps are extremely common, with 56–94% of the population being stung at least once in their lifetime. The complex process of venom activity and inflammation causes local reactions with pain and pruritus, sometimes anaphylactic reactions and more seldomly, as in case of numerous stings, systemic intoxication. We reviewed the literature regarding itch experienced after Hymenoptera stings, but found no study that placed a specific focus on this topic. Hymenoptera venoms are composed of many biologically active substances, including peptide toxins and proteinaceous toxins. Peptide toxins from bee venom cause cell lysis and ion channel modulation in the peripheral and central nervous systems, while toxins from wasp venom induce mast cell degranulation and chemotaxis of polymorphonuclear leukocytes in the skin. The proteinaceous toxins cause a disruption of the cell membranes and necrotic cell death, degradation of hyaluronan (an extracellular matrix glycosaminoglycan), increased vascular permeability, hemolysis, as well as activated platelet aggregation. Mediators which could be directly involved in the venom-induced pruritus include histamine and tryptase released from mast cells, interleukin-4 and interleukin-13 from Th2 lymphocytes, as well as leukotriene C4. We postulate that a pruriceptive itch is induced due to the pharmacological properties of Hymenoptera venoms.

A Novel Insecticidal Spider Peptide that Affects the Mammalian Voltage-Gated Ion Channel hKv1.5

Spider venoms include various peptide toxins that modify the ion currents, mainly of excitable insect cells. Consequently, scientific research on spider venoms has revealed a broad range of peptide toxins with different pharmacological properties, even for mammal species. In this work, thirty animal venoms were screened against hKv1.5, a potential target for atrial fibrillation therapy. The whole venom of the spider Oculicosa supermirabilis, which is also insecticidal to house crickets, caused voltage-gated potassium ion channel modulation in hKv1.5. Therefore, a peptide from the spider O. supermirabilis venom, named Osu1, was identified through HPLC reverse-phase fractionation. Osu1 displayed similar biological properties as the whole venom; so, the primary sequence of Osu1 was elucidated by both of N-terminal degradation and endoproteolytic cleavage. Based on its primary structure, a gene that codifies for Osu1 was constructed de novo from protein to DNA by reverse translation. A recombinant Osu1 was expressed using a pQE30 vector inside the E. coli SHuffle expression system. recombinant Osu1 had voltage-gated potassium ion channel modulation of human hKv1.5, and it was also as insecticidal as the native toxin. Due to its novel primary structure, and hypothesized disulfide pairing motif, Osu1 may represent a new family of spider toxins.

Structures of the AMPA receptor in complex with its auxiliary subunit cornichon

In the brain, AMPA-type glutamate receptors (AMPARs) form complexes with their auxiliary subunits and mediate the majority of fast excitatory neurotransmission. Signals transduced by these complexes are critical for synaptic plasticity, learning, and memory. The two major categories of AMPAR auxiliary subunits are transmembrane AMPAR regulatory proteins (TARPs) and cornichon homologs (CNIHs); these subunits share little homology and play distinct roles in controlling ion channel gating and trafficking of AMPAR. Here, I report high-resolution cryo–electron microscopy structures of AMPAR in complex with CNIH3. Contrary to its predicted membrane topology, CNIH3 lacks an extracellular domain and instead contains four membrane-spanning helices. The protein-protein interaction interface that dictates channel modulation and the lipids surrounding the complex are revealed. These structures provide insights into the molecular mechanism for ion channel modulation and assembly of AMPAR/CNIH3 complexes.

Nociceptor Signalling through ion Channel Regulation via GPCRs

The prime task of nociceptors is the transformation of noxious stimuli into action potentials that are propagated along the neurites of nociceptive neurons from the periphery to the spinal cord. This function of nociceptors relies on the coordinated operation of a variety of ion channels. In this review, we summarize how members of nine different families of ion channels expressed in sensory neurons contribute to nociception. Furthermore, data on 35 different types of G protein coupled receptors are presented, activation of which controls the gating of the aforementioned ion channels. These receptors are not only targeted by more than 20 separate endogenous modulators, but can also be affected by pharmacotherapeutic agents. Thereby, this review provides information on how ion channel modulation via G protein coupled receptors in nociceptors can be exploited to provide improved analgesic therapy.

Isopropyl Caffeate: A Caffeic Acid Derivative—Antioxidant Potential and Toxicity

Phenolic compounds, among them isopropyl caffeate, possess antioxidant potential, but not without toxicity and/or adverse effects. The present study aimed to evaluate the antioxidant activity and toxicity of isopropyl caffeate through in silico, in vitro and in vivo testing. The results showed that isopropyl caffeate presents no significant theoretical risk of toxicity, with likely moderate bioactivity: GPCR binding, ion channel modulation, nuclear receptor binding, and enzyme inhibition. Isopropyl caffeate induced hemolysis only at the concentrations of 500 and 1000 μg/ml. We observed types A and O erythrocyte protection from osmotic stress, no oxidation of erythrocytes, and even sequestrator and antioxidant behavior. However, moderate toxicity, according to the classification of GHS, was demonstrated through depressant effects on the central nervous system, though there was no influence on water and food consumption or on weight gain, and it did present possible hepatoprotection. We conclude that the effects induced by isopropyl caffeate are due to its antioxidant activity, capable of preventing production of free radicals and oxidative stress, a promising molecule with pharmacological potential.