PL-3994

PL-3994 is a natriuretic peptide receptor-A (NPR-A) agonist that is resistant to neutral endopeptidase and acts as a bronchodilator. PL-3994 produces concentration-dependent relaxation of pre-contracted guinea-pig trachea with an IC50 value of 42.7 nM[1].

Research Areas >> Others

Signaling Pathways >> Others >> Others

PL-3994 has high affinity for recombinant human, dog, or rat NPR-As with Ki values of 1 nM, 41 nM, 10 nM, respectively. And PL-3994 binds to hNPR-C with Ki of 7 nM, while there is no effect on cGMP generation in hNPR-B[1]. PL-3994 induces dose-dependent cGMP generation in human, dog, and rat NPR-As with EC50s of 2 nM, 3 nM, and 14 nM, respectively[1]. PL-3994 (0.1 nM-100 mM; 5-20 min) elicits a potent, concentration-dependent but small relaxation of pre-contracted human precision-cut lung slices (hPCLS)[1].

Intratracheal PL-3994 (1-1000 mg/kg; i.t.; single dose) produces a dose-dependent inhibition of the bronchoconstrictor response evoked by aerosolized methacholine, without significant effect on cardiovascular parameters[1]. PL-3994 is resistant to degradation by human neutral endopeptidase (hNEP) (92% remaining after 2 h), whereas the natural ligands, ANP and CNP, are rapidly metabolized (≤1% remaining after 2 h)[1]. Animal Model: Guinea-pig model anaesthetized with urethane (1.75 g/kg, i.p.)[1] Dosage: 1, 10, 100, 1000 mg/kg Administration: Intrathecal; single dose Result: Resulted a significant maximum inhibition of 43%, 63% and 70%, respectively, observed after 15-min pretreatment at doses of 10, 100 and 1000 mg/kg.