Inhibition of substance P-induced vascular leakage in rat by N-acetyl-neurotensin-(8-13).
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.
Gao
G C
GC
School of Public Health, University of California at Berkeley 94720, USA.
Wei
E T
ET
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004947:Esophagus / Q000098:blood supply / Q000187:drug effects; D005215:Fasting; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000494:pharmacology; D009928:Organ Specificity; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001743:Urinary Bladder / Q000098:blood supply / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D013373:Substance P; D009496:Neurotensin; C034659:acetylneurotensin (8-13); C066892:CP 96345