Co-regulation of mucosal prostanoids and substance P by indomethacin in rat stomachs.
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.
Ko
J K
JK
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong.
Tang
F
F
Cho
C H
CH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016718:Arachidonic Acid; D013373:Substance P; C032132:substance P, prolyl(2)-tryptophan(7,9)-; D015232:Dinoprostone; D007213:Indomethacin