FIGURE 2.

Mechanism of PnTx2-6 toxin and PnPP-19 peptide in the corpus cavernosum. Red arrows indicate PnTx2-6 actions and green arrows indicate PnPP-19 actions. The neuronal depolarization caused by PnTx2-6 (by delay Na⁺ channel inactivation current) leads to the opening of N-type Ca²⁺ channels, increasing its influx. Increase in intracellular Ca²⁺ triggers the NO production and availability. NO production stimulates guanylate cyclase enzyme (GCs), rising cGMP, which stimulates PKG resulting in blockade of Cavs channels and opening of Kvs channels. The aftermath is decreased Ca²⁺ inside the smooth muscle cell leading to relaxation and penile erection. Also, PnTx2-6 does not inhibit the action of the enzyme PDE-5. PnPP-19 (green arrows) increases NO and cGMP via nNOS and iNOS activation. PnPP-19 promotes CC relaxation without acting on voltage-dependent Na⁺ channels, neither N-type Ca²⁺ channels, and as PnTx2-6 it does not inhibit the action of PDE-5 or exerts an effect on Ach. Abbreviations: PKG, protein kinase G; GTP, guanosine triphosphate; nNOS, neuronal nitric oxide synthase; iNOS, induced nitric oxide synthase; CaM, calmodulin; NANC, nitrergic nerves; PDE-5, phosphodiesterase-5 enzyme; cGMP, cyclic guanosine monophosphate; NO, nitric oxide; GCs, soluble Guanylate cyclase. Created with BioRender.com.