Co-regulation of mucosal prostanoids and substance P by indomethacin in rat stomachs

Life Sci. 1997;60(19):PL 277-81. doi: 10.1016/s0024-3205(97)00117-3.

Abstract

The present investigation examined the correlation between the regulation of mucosal prostaglandin (PG) biosynthesis and the release of the neuropeptide substance P (SP) in rat stomachs by indomethacin, a cyclooxygenase inhibitor. When given subcutaneously at the dose of 5 mg/kg, indomethacin reduced mucosal biosynthesis of PGE2 and concurrently lowered mucosal SP level. The inter-relationship between mucosal generation of PG and SP was further demonstrated by using [D-Pro2, D-Trp7,9]-SP, which also inhibited PGE2 production besides its suppression on SP release. Co-administration of either arachidonic acid, the PGE2 precursor, or SP reversed the inhibitory actions of indomethacin and [D-Pro2, D-Trp7,9]-SP, respectively, on mucosal levels of PGE2 and SP. Our findings suggest that indomethacin, aside from its depletion of endogenous PG, also exerts a secondary action in regulating the release of SP, which is mediated indirectly through PG in the gastric mucosa. These actions may play a role in the modulation of gastric mucosal integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Arachidonic Acid / pharmacology
  • Dinoprostone / biosynthesis*
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / metabolism
  • Indomethacin / pharmacology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Substance P / analogs & derivatives
  • Substance P / metabolism*
  • Substance P / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Arachidonic Acid
  • Substance P
  • substance P, prolyl(2)-tryptophan(7,9)-
  • Dinoprostone
  • Indomethacin