Amazing stuff! This is a rather speculative outlook, but who knows ...
"... A team ... has for the first time shown that the venom’s effect is likely due to one peptide attacking several pain receptors at once. ...
‘The real challenge ... will be to redesign the peptide to reverse its activity – blocking sodium channels and opening of potassium channels,’ ... ‘If this can be achieved, that would be a new generation of potential analgesics.’ ... calls a molecule that could perform this opposite function ‘the perfect analgesic’. ...
Despite several decades of research, venoms are still an untapped source of pharmacological treasures ... ‘[Some venoms] have taught us, for example, which targets are important to treat in irritable bowel syndrome ..."
‘The real challenge ... will be to redesign the peptide to reverse its activity – blocking sodium channels and opening of potassium channels,’ ... ‘If this can be achieved, that would be a new generation of potential analgesics.’ ... calls a molecule that could perform this opposite function ‘the perfect analgesic’. ...
Despite several decades of research, venoms are still an untapped source of pharmacological treasures ... ‘[Some venoms] have taught us, for example, which targets are important to treat in irritable bowel syndrome ..."
From the abstract:
"The King Baboon spider, Pelinobius muticus, is a burrowing African tarantula. Its impressive size ... Hyperalgesia is the most prominent symptom after bites from P. muticus, but the molecular basis by which the venom induces pain is unknown. Proteotranscriptomic analysis of P. muticus venom uncovered a cysteine-rich peptide, δ/κ-theraphotoxin-Pm1a (δ/κ-TRTX-Pm1a), that elicited nocifensive behavior when injected into mice. In small dorsal root ganglion neurons, synthetic δ/κ-TRTX-Pm1a (sPm1a) induced hyperexcitability by enhancing tetrodotoxin-resistant sodium currents, impairing repolarization and lowering the threshold of action potential firing, consistent with the severe pain associated with envenomation. The molecular mechanism of nociceptor sensitization by sPm1a involves multimodal actions over several ion channel targets, including NaV1.8, KV2.1, and tetrodotoxin-sensitive NaV channels. The promiscuous targeting of peptides like δ/κ-TRTX-Pm1a may be an evolutionary adaptation in pain-inducing defensive venoms."
No comments:
Post a Comment