title: Cell-penetrating peptides modulate the vascular action of phenylephrine.
abstract: Cell-penetrating peptides (CPP) are a family of peptides able to penetrate the cell membrane. This group of compounds has attracted consideration as potential therapeutic tools for the delivery of various substances into cells. Here, we investigated possible interactions between several CPP synthesized in our laboratory and the vascular action of phenylephrine. We used isolated rat tail artery and examined the influence of pretreatment by seven different CPP on the concentration-response curve induced by the α1 receptor agonist phenylephrine. Peptides were synthesized by solid-phase peptide synthesis (SPPS) using the 9-fluorenylmethoxycarbonyl (Fmoc) method. Among the seven different polypeptides, i.e., TP10 (transportan-10), [Lys(AAc)13]TP, [Lys(CAc)13]TP, [Lys(GAc)13]TP, [Lys(TAc)13]TP, [Lys(UAc)13]TP and [Lys(Ac)13]TP, only TP10 and [Lys(AAc)13]TP, both at a concentration of 1 μM (the lowest concentration inducing a significant change in the contraction of isolated rat stomach in our pilot study), rendered rat tail artery more sensitive to phenylephrine; the relative potency increased significantly. Conversely, [Lys(Ac)13]TP strongly decreased the efficacy of phenylephrine.
authors: Department of Pharmacology, Medical University of Gdańsk, Dębowa 23, PL 80-204 Gdańsk, Poland. ikocic@gumed.edu.pl
authors: Ivan
authors: I
authors: Kocić
authors: Jarosław
authors: J
authors: Ruczyński
authors: Renata
authors: R
authors: Szczepańska
authors: Mariola
authors: M
authors: Olkowicz
authors: Brygida
authors: B
authors: Parfianowicz
authors: Izabela
authors: I
authors: Rusiecka
authors: Piotr
authors: P
authors: Rekowski
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005449:Fluorenes / Q000737:chemistry; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology*; D010865:Pilot Projects; D051381:Rats; D017208:Rats, Wistar; D013623:Tail / Q000098:blood supply; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: C496789:9-fluorenylmethoxycarbonyl; D058646:Adrenergic alpha-1 Receptor Agonists; D057846:Cell-Penetrating Peptides; D005449:Fluorenes; D014662:Vasoconstrictor Agents; D010656:Phenylephrine