Inhibition of substance P-induced vascular leakage in rat by N-acetyl-neurotensin-(8-13).

摘要

Substance P (SP) administered 40 micrograms/kg s.c. to pentobarbital-anesthetized rats induced salivation and leakage of plasma constituents into the skin, muscle, trachea, esophagus and bladder, as measured by Monastral blue B labeling of small blood vessels or by extravasation of Evans blue dye into tissues. These SP effects were inhibited by N-acetyl-neurotensin-(8-13) (Ac-NT-(8-13)) and by CP-96,345, a nonpeptide SP receptor antagonist. Intralumenal injection of Ac-NT-(8-13) or CP-96,345 into the bladder reduced SP-induced leakage of Evans blue dye but not dye leakage into the pawskin, indicating a localised drug action. Ac-NT-(8-13) appears to act directly on discrete sites in skin and in mucous membranes to functionally antagonize the inflammatory effects of SP.