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 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.