N-Salicyloyltryptamine, an N-Benzoyltryptamine Analogue, Induces Vasorelaxation through Activation of the NO/sGC Pathway and Reduction of Calcium Influx.

Autor:	Veras, Robson Cavalcante, Silva, Darizy Flávia, Bezerra, Lorena Soares, Assis, Valéria Lopes de, Vasconcelos, Walma Pereira de, Alustau, Maria do Carmo, Albuquerque, José George Ferreira de, Furtado, Fabíola Fialho, Araújo, Islania Giselia de Albuquerque, Azevedo, Fátima de Lourdes Assunção Araújo de, Ribeiro, Thais Porto, Barbosa-Filho, José Maria, Gutierrez, Stanley Juan Chavez, Medeiros, Isac Almeida
Předmět:	BIOCHEMICAL mechanism of action MESENTERIC artery NITRIC oxide FLOW cytometry SYNTHASES VOLTAGE-gated ion channels
Zdroj:	Molecules; Feb2018, Vol. 23 Issue 2, p253, 12p, 5 Graphs
Abstrakt:	Benzoyltryptamine analogues act as neuroprotective and spasmolytic agents on smooth muscles. In this study, we investigated the ability of N-salicyloyltryptamine (STP) to produce vasorelaxation and determined its underlying mechanisms of action. Isolated rat mesenteric arteries with and without functional endothelium were studied in an isometric contraction system in the presence or absence of pharmacological inhibitors. Amperometric experiments were used to measure the nitric oxide (NO) levels in CD31+ cells using flow cytometry. GH3 cells were used to measure Ca2+ currents using the whole cell patch clamp technique. STP caused endothelium-dependent and -independent relaxation in mesenteric rings. The endothelial-dependent relaxations in response to STP were markedly reduced by L-NAME (endothelial NO synthase—eNOS—inhibitor), jHydroxocobalamin (NO scavenger, 30 µM) and ODQ (soluble Guanylyl Cyclase—sGC—inhibitor, 10 µM), but were not affected by the inhibition of the formation of vasoactive prostanoids. These results were reinforced by the increased NO levels observed in the amperometric experiments with freshly dispersed CD31+ cells. The endothelium-independent effect appeared to involve the inhibition of voltage-gated Ca2+ channels, due to the inhibition of the concentration-response Ca2+ curves in depolarizing solution, the increased relaxation in rings that were pre-incubated with high extracellular KCl (80 mM), and the inhibition of macroscopic Ca2+ currents. The present findings show that the activation of the NO/sGC/cGMP pathway and the inhibition of gated-voltage Ca2+ channels are the mechanisms underlying the effect of STP on mesenteric arteries. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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