Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider.

The King Baboon spider, , is a burrowing African tarantula. Its impressive size and appealing coloration are tempered by reports describing severe localized pain, swelling, itchiness, and muscle cramping after accidental envenomation. Hyperalgesia is the most prominent symptom after bites from , but the molecular basis by which the venom induces pain is unknown.

Discovery and mode of action of a novel analgesic β-toxin from the African spider Ceratogyrus darlingi.

Spider venoms are rich sources of peptidic ion channel modulators with important therapeutical potential. We screened a panel of 60 spider venoms to find modulators of ion channels involved in pain transmission. We isolated, synthesized and pharmacologically characterized Cd1a, a novel peptide from the venom of the spider Ceratogyrus darlingi.

The tarantula toxin β/δ-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity.

Voltage-gated sodium (Na) channels are essential for the transmission of pain signals in humans making them prime targets for the development of new analgesics. Spider venoms are a rich source of peptide modulators useful to study ion channel structure and function. Here we describe β/δ-TRTX-Pre1a, a 35-residue tarantula peptide that selectively interacts with neuronal Na channels inhibiting peak current of hNa1.

Pharmacological characterisation of the highly Na1.7 selective spider venom peptide Pn3a.

Human genetic studies have implicated the voltage-gated sodium channel Na1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits Na1.

Analgesic Effects of GpTx-1, PF-04856264 and CNV1014802 in a Mouse Model of NaV1.7-Mediated Pain.

Loss-of-function mutations of Na(V)1.7 lead to congenital insensitivity to pain, a rare condition resulting in individuals who are otherwise normal except for the inability to sense pain, making pharmacological inhibition of Na(V)1.7 a promising therapeutic strategy for the treatment of pain.

Characterisation of Na(v) types endogenously expressed in human SH-SY5Y neuroblastoma cells.

The human neuroblastoma cell line SH-SY5Y is a potentially useful model for the identification and characterisation of Na(v) modulators, but little is known about the pharmacology of their endogenously expressed Na(v)s. The aim of this study was to determine the expression of endogenous Na(v) α and β subunits in SH-SY5Y cells using PCR and immunohistochemical approaches, and pharmacologically characterise the Na(v) isoforms endogenously expressed in this cell line using electrophysiological and fluorescence approaches. SH-SY5Y human neuroblastoma cells were found to endogenously express several Na(v) isoforms including Na(v)1.

Apratoxin D, a potent cytotoxic cyclodepsipeptide from papua new guinea collections of the marine cyanobacteria Lyngbya majuscula and Lyngbya sordida.

Cancer cell toxicity-guided fractionation of extracts of the Papua New Guinea marine cyanobacteria Lyngbya majuscula and Lyngbya sordida led to the isolation of apratoxin D (1). Compound 1 contains the same macrocycle as apratoxins A and C but possesses the novel 3,7-dihydroxy-2,5,8,10,10-pentamethylundecanoic acid as the polyketide moiety. The planar structures and stereostructures of compound 1 were determined by extensive 1D and 2D NMR and MS data analyses and by comparison with the spectroscopic data of apratoxins A and C.