In vitro effects of arachidonic acid on the prostaglandin synthesizing system in gastric mucosa.
Self-destruction of the prostaglandin cyclooxygenase has been suggested to be an important factor in the regulation of endogenous prostaglandin synthesis. The present study was done in order to define the role of this substrate-induced inactivation in the regulation of prostaglandin synthesis in gastric mucosa. In tissue homogenate, the prostaglandin synthesizing capacity is rapidly inactivated at 37 degrees C, even in the absence of exogenous arachidonic acid. It was shown that this inactivation can be prevented both by EDTA as a chelator of calcium-ions and by tetracaine, a specific inhibitor of the phospholipase A2. Additional exogenous arachidonic acid again inactivated prostaglandin synthesis in a dose dependent manner. In contrast, the prostaglandin synthesizing capacity in organ cultured mucosal biopsies is well preserved, although the release of endogenous substrate was activated by extracellular calcium and Ca-ionophore A23187. Furthermore, even at high concentrations of exogenous arachidonic acid present in the culture medium, the synthesizing capacity in intact biopsies was only slightly and reversibly reduced. These large differences between intact biopsies and cell free tissue preparations point to very efficient mechanisms controlling the substrate availability for the cyclooxygenase system both from endogenous and exogenous sources in intact gastric mucosa.
Preclik
G
G
University of Ulm, Department of Internal Medicine II, Germany.
Stange
E F
EF
Arnold
D
D
Ditschuneit
H
H
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D009924:Organ Culture Techniques; D011453:Prostaglandins / Q000096:biosynthesis* / Q000378:metabolism; D011817:Rabbits; D011863:Radioimmunoassay; D013748:Tetracaine / Q000494:pharmacology; D014020:Tissue Extracts
D001095:Arachidonic Acids; D011453:Prostaglandins; D014020:Tissue Extracts; D013748:Tetracaine; D016718:Arachidonic Acid; D003513:Cycloheximide; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D002122:Calcium Chloride