Cholinergic modulation of substance P release

This study was initiated to evaluate mechanisms of release of immunoreactive substance P into the peripheral circulation and to determine whether these mechanisms are subject to cholinergic modulation. In conscious dogs, a high-protein meal significantly increased plasma concentrations of immunoreactive substance P from basal levels of 13.7±1.8 pg/ml to a peak of 20.1±2.8 pg/ml at 30 min after which they returned to baseline. Prior atropinization (200 mg/kg) abolished this response and lowered the plasma levels to a nadir of 2.2 pg/ml at 20 min. Similarly, infusion of bombesin (17 ng/kg/min) increased peripheral venous substance P levels by 768±155 pg-min/ml for 120 min, whereas after prior treatment with atropine, bombesin released no significant amounts of this peptide (–10±134 pg-min/ml). The data support the concept that substance P release is under cholinergic control.Supported in part by U.S.P.H.S. Grant 5-R01 AM26522 from the N.I.A.M.D.D. and The Foundation for Surgical Education and Investigation.