Phenylephrine hydrochloride (NCI-c55641) is a selective agonist of the α1-adrenergic receptor.

Phenylephrine protects cardiomyocytes from serum deprivation and hypoxia. It induces rapid translocation of PKC-epsilon (EC 50= 0.9 mM), with a lesser fraction lost compared to ET-1, and prevents downregulation of Bcl-X and Bcl-2 mRNA/proteins while inducing hypertrophic growth. Phenylephrine dose-dependently increases contractile force in hyperosmotic cells at pCa 7, which is reversible upon phentolamine addition. The protective effects mediated by Phenylephrine are inhibited by the PI 3-kinase inhibitor wortmannin and mimicked by the caspase-9 peptide inhibitor LEHD-fmk. It stimulates phosphoinositide hydrolysis, cellular growth, and expression of various genes associated with cardiac hypertrophy, such as atrial natriuretic factor. Phenylephrine-induced NOi release requires stimulation by IP3 and PI-3K/Akt-dependent calcium signaling, and it also enhances localized sarcoplasmic reticulum calcium release through IP3-dependent signaling. Induction of NOi release by Phenylephrine is inhibited by 1 mM prazocin, 10 mM W-7, 10 mM L-NIO, 10 mM LY294002, 2 mM H-89, 5 mM thapsigargin, 10 mM ryanodine, 2 mM 2-APB, or 10 mM xestospongin C. Additionally, 1 μM Phenylephrine significantly enhances HGF-induced hepatocyte DNA synthesis and proliferation. Finally, 1 mM Phenylephrine reversibly increases peak I(Ca,L) by 51.3% (N=40) and shifts the activation voltage by -10 mV.