Up-regulation of prostaglandin E2 binding and of prostanoid release in rabbits producing antibodies against prostaglandin E2.
German Giant rabbits successfully immunized against prostaglandin (PG) E2 as shown by a rise in antibody titers developed gastric mucosal lesions. Enzymatically dispersed gastric mucosal cells of these animals had a significantly enhanced production of PG E2 and PG I2 as measured by specific radioimmunoassays. This may be explained by an increased supply with endogenous arachidonic acid (as indicated by an enhanced phospholipase A2/LAT ratio) and by a higher activity of the subsequent PG forming enzymes (as indicated by a more effective stimulation of PG production by exogenous arachidonic acid). Gastric mucosal plasma membranes of immunized rabbits had significantly higher PG E2 binding capacity (108 +/- 9 fmol/mg protein) than those of nonimmunized rabbits (72 +/- 5 fmol/mg protein). The ligand affinity was not affected by immunization. Neither histamine-stimulated 14C-amino-pyrine uptake of isolated parietal cells as a marker for acid production nor its inhibition by PG E2 were influenced by receptor up-regulation. The increased eicosanoid release can be regarded as an endogenous defense mechanism against increased mucosal vulnerability caused by PG E2 scavenging. The potential role of PG E2 receptor up-regulation in support of this process remains to be established.
Beinborn
M
M
Abteilung Allgemeine Pharmakologie, Medizinische Hochschule Hannover, FRG.
Hell
M
M
Seidler
U
U
Sewing
K F
KF
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000917:Antibody Formation; D001095:Arachidonic Acids / Q000494:pharmacology; D015232:Dinoprostone / Q000276:immunology / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008297:Male; D010295:Parietal Cells, Gastric / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D013276:Stomach Ulcer / Q000209:etiology / Q000378:metabolism*
D001095:Arachidonic Acids; D008244:Lysophosphatidylcholines; D011982:Receptors, Prostaglandin; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone; D007213:Indomethacin