Rat aorta relaxation induced by the venom of Poecilotheria regalis involves the activation of the NO/cGMP pathway

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

“…A previous study revealed vasodilatory peptide toxins in P. regalis venom. However, neither their identity nor their mechanism of action was described ( Díaz-Peña et al, 2019 ). Here, the vasodilatory peptide fraction B, obtained from the venom of P. regalis , induced a long-lasting vasodilatory effect, consistent with properties described for this tarantula's venom, as is the case for vasodilatory peptides from venoms of hematophagous animals ( Grevelink et al, 1995 ; Jackson et al, 1996 ).…”

“…The vasodilatory activity was assayed in rat aortic ring preparations in organ bath tension measurements, based on Díaz-Peña et al (2019) . After contraction induced by phenylephrine hydrochloride (Phe, 1 μM; PHR1017, Supelco) reached a sustained action, lyophilized fractions obtained from high-performance liquid chromatography (HPLC) were reconstituted in Krebs-Henseleit solution or HPLC grade water (JT Baker), gently stirred, and added to each organ bath chamber.…”

“…Separation was achieved by using a linear gradient ranging from 100% Phase A (0.1% aqueous trifluoroacetic acid) to 40% Phase B (100% acetonitrile), with an increasing rate of 0.67% per minute. Previous to the linear gradient, Phase A was held constant for 7 min to allow non-peptide compounds with vasodilatory action to elute from the column, as stated by Díaz-Peña et al (2019) . The flow rate was set at 1 ml/min, and eluates were monitored at 215 nm with a photodiode array detector (Waters 2998).…”

“…Nonetheless, some properties of these vasodilator compounds do not fit with properties induced by vasodilator venoms, suggesting that other compounds contained in venoms may contribute ( Horta et al, 2013 ). Indeed, a peptide-rich fraction obtained from the venom of the tarantula Poecilotheria regalis was found to induce a potent vasodilatory effect on precontracted rat aortic rings, indicating that DRPs may also contribute to venom propagation ( Díaz-Peña et al, 2019 ). Additionally, recent reports indicate that hyaluronidases from scorpion venoms hydrolyzes hyaluronic acid located in vascular endothelial barriers, suggesting a possible synergistic action with vasodilatory toxins in venom biodistribution ( de Oliveira-Mendes et al, 2019 ).…”

“…The Inhibitory Cystine Knot (ICK) peptide ( Craik et al, 2001 ) M-TRTX-Gr1a or GsMTx4, isolated from the venom of Grammostola rosea , is the only characterized DRP with potential vasodilatory action, since it has been used as a pharmacological tool to attenuate pressure-induced changes in rat cerebral arteries ( Lee et al, 2007 ); however, its direct vasodilatory action has not been investigated. Also, even though a peptides-containing fraction obtained from the venom of the tarantula P. regalis was found to induce a direct vasodilatory effect, neither the identity of these peptides nor their mechanism of action was described ( Díaz-Peña et al, 2019 ). This work characterizes the mechanism of action and sequence of the vasodilatory peptides obtained from the venom of the tarantula P. regalis .…”