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 α 1 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.