title: Structure-related blockage of calcium channels by vasodilator alkamides in mice mesenteric artery.
abstract: The development of new calcium channel blockers is still relevant for the understanding of their physiological role and pharmacological and therapeutic purposes. For this task, natural products represent a relevant source of new drugs. The present work investigated the mechanism and the structural relationship of the vasodilator effect of riparins I, II and III in mouse small mesenteric artery. Riparins I, II and III induced an endothelium-independent and concentration-dependent vasodilator effect in mesenteric arteries. Riparins II and III were more potent than riparin I, suggesting a structural relationship of the effect of these drugs. All riparins inhibited the contractile effect of KCl, similarly to nifedipine. However, the inhibitory profile was different for the contractile responses to phenylephrine and caffeine, passing from similar to nifedipine with riparin I, for similar to SKF-96365 with riparin III. A comparable effect was observed for the increase in the intracellular calcium concentration induced by caffeine and phenylephrine. These results suggest that the higher hydroxylation provides the alkamides the ability to inhibit non-selective cation channels in addition to the inhibition of L-type calcium channels in mouse mesenteric arteries. These observations may give support to the development of new selective inhibitors of non-selective cation channels using alkamides as leading compounds.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Daniela C G
authors.initials: DC
authors.lastname: Garcia
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Aline C
authors.initials: AC
authors.lastname: Pereira
authors.affiliation: Laboratory Chemistry of Bioactive Natural and Synthetic Products, Universidade Federal do Piauí, Teresina, PI, Brazil.
authors.forename: Stanley J C
authors.initials: SJ
authors.lastname: Gutierrez
authors.affiliation: Laboratory of Pharmaceutical Technology, Universidade Federal da Paraíba, Brazil.
authors.forename: José Maria
authors.initials: JM
authors.lastname: Barbosa-Filho
authors.affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Virgínia S
authors.initials: VS
authors.lastname: Lemos
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil. Electronic address: sfcortes@icb.ufmg.br.
authors.forename: Steyner F
authors.initials: SF
authors.lastname: Côrtes
mesh_terms: D000818:Animals; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014439:Tyramine / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001549:Benzamides; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; C521850:N-(2-hydroxybenzoyl)tyramine; D014665:Vasodilator Agents; C087987:riparin III; D014439:Tyramine
keywords: Calcium channels; Mesenteric artery; Non-selective cation channels; Riparins; Vasodilatation