A subfraction obtained from the venom of the tarantula Poecilotheria regalis contains inhibitor cystine knot peptides and induces relaxation of rat aorta by inhibiting L-type voltage-gated calcium channels
Luis Fernando Díaz-Peña,
Torres-Ortiz Daniela,
Manuel B. Aguilar,
Enoch Luis,
Fernando Lazcano-Pérez,
Roberto Arreguín-Espinosa,
Arturo Hernandez-Cruz,
César Ibarra-Alvarado,
Alejandro García-Arredondo
Affiliations
Luis Fernando Díaz-Peña
Posgrado en Ciencias Químico Biológicas, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario S/N, 76010, Querétaro, Querétaro, Mexico
Torres-Ortiz Daniela
Posgrado en Ciencias Químico Biológicas, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario S/N, 76010, Querétaro, Querétaro, Mexico
Manuel B. Aguilar
Laboratorio de Neurofarmacología Marina, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, 76230, Mexico
Enoch Luis
Cátedras CONACYT, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, 04510, Ciudad de México, Mexico; Laboratorio Nacional de Canalopatías, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad de México, Mexico
Fernando Lazcano-Pérez
Laboratorio de Química de Biomacromoléculas, Instituto de Química, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
Roberto Arreguín-Espinosa
Laboratorio de Química de Biomacromoléculas, Instituto de Química, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
Arturo Hernandez-Cruz
Laboratorio Nacional de Canalopatías, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad de México, Mexico
César Ibarra-Alvarado
Departamento de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario S/N, 76010, Querétaro, Querétaro, Mexico
Alejandro García-Arredondo
Departamento de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario S/N, 76010, Querétaro, Querétaro, Mexico; Corresponding author.
Venoms from tarantulas contain low molecular weight vasodilatory compounds whose biological action is conceived as part of the envenomation strategy due to its propagative effects. However, some properties of venom-induced vasodilation do not match those described by such compounds, suggesting that other toxins may cooperate with these ones to produce the observed biological effect. Owing to the distribution and function of voltage-gated ion channels in blood vessels, disulfide-rich peptides isolated from venoms of tarantulas could be conceived into potential vasodilatory compounds. However, only two peptides isolated from spider venoms have been investigated so far. This study describes for the first time a subfraction containing inhibitor cystine knot peptides, PrFr-I, obtained from the venom of the tarantula Poecilotheria regalis. This subfraction induced sustained vasodilation in rat aortic rings independent of vascular endothelium and endothelial ion channels. Furthermore, PrFr-I decreased calcium-induced contraction of rat aortic segments and reduced extracellular calcium influx to chromaffin cells by the blockade of L-type voltage-gated calcium channels. This mechanism was unrelated to the activation of potassium channels from vascular smooth muscle, since vasodilation was not affected in the presence of TEA, and PrFr-I did not modify the conductance of the voltage-gated potassium channel Kv10.1. This work proposes a new envenomating function of peptides from venoms of tarantulas, and establishes a new mechanism for venom-induced vasodilation.
