title: Moving pieces in a cryptomic puzzle: Cryptide from Tityus serrulatus Ts3 Nav toxin as potential agonist of muscarinic receptors.
abstract: Cryptome is as a subset of a given proteome containing bioactive cryptides embedded in larger peptides or proteins. We pinpointed a striking sequence similarity between two peptides from the Tityus serrulatus venom: Ts10 (KKDGYPVEYDRAY) and the N-terminal of Ts3 (KKDGYPVEYDNCAY). Ts3 (former Tityustoxin or TsIV) is an α-neurotoxin acting on voltage-gated sodium channels while Ts10 (former Peptide T) is a bradykinin-potentiating peptide and was originally reported as inhibitor of the angiotensin-converting enzyme (ACEi). Thus, the goal of this study was to evaluate whether such peptide hidden in the N-terminal of Ts3 (Ts31-14[C12S]) was able to mimic known effects of Ts10 as well as to expand the current knowledge of the vascular effects and molecular targets of these peptides. Similar to Ts10, Ts31-14[C12S]was able to potentiate the hypotensive effect of bradykinin (BK). However, none of these peptides was able to induce a long-lasting BK-potentiating effect, suggesting that this effect may not be their main biological outcome. On the other hand, we report that Ts10 and mainly Ts31-14[C12S]induced a strong vasodilation effect depending on the presence of functional endothelium and nitric oxide (NO) production. Unlike previously reported, Ts10 was not able to inhibit ACE activity (similar result was observed for Ts31-14[C12S]). On the other hand, we report that Ts31-14[C12S]induces vasodilation via the activation of muscarinic acetylcholine receptors (mAChRs) M2 and M3 while only the activation of mAChR M2 seems to be required for Ts10-induced vasodilation.
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Cibele
authors.initials: C
authors.lastname: Rocha-Resende
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Nádia Miricéia
authors.initials: NM
authors.lastname: Leão
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: de Lima
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Robson Augusto
authors.initials: RA
authors.lastname: Santos
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: apimenta@icb.ufmg.br.
authors.forename: Adriano Monteiro de Castro
authors.initials: AMC
authors.lastname: Pimenta
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: tvbraga@icb.ufmg.br.
authors.forename: Thiago
authors.initials: T
authors.lastname: Verano-Braga
mesh_terms: D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008297:Male; D023421:Models, Animal; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000819:agonists*; D043587:Receptor, Muscarinic M3 / Q000819:agonists*; D012604:Scorpion Venoms / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D061566:Voltage-Gated Sodium Channels / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D012604:Scorpion Venoms; C485970:Ts3 toxin, Tityus serrulatus; D014665:Vasodilator Agents; D061566:Voltage-Gated Sodium Channels; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin
keywords: Bradykinin receptor; Bradykinin-potentiating peptides; Muscarinic acetylcholine receptor; Tityus serrulatus