Adrenergic regulation of prostaglandin biosynthesis in cultured rabbit gastric epithelial cells.
Adrenergic regulation of prostaglandin (PG) biosynthesis was investigated in 1-14C-arachidonic acid-prelabeled cultured rabbit gastric epithelial cells (RGECs). RGECs expressed adrenergic alpha 1- and beta-receptors and muscarinic receptors. Norepinephrine facilitated the synthesis of PGs I2 (determined as the stable metabolite 6-keto PGF1 alpha) and E2 and hydroxyfatty acids, while epinephrine facilitated the synthesis of PGI2 and hydroxyfatty acids, but not PGE2. However, isoproterenol did not affect PG biosynthesis. The effects of norepinephrine and epinephrine on PG biosynthesis were markedly suppressed by the non-selective alpha-blocker phentolamine and/or the selective alpha 1-blocker prazosin. In combination with epinephrine, the selective alpha 2-blocker yohimbine or the beta-blocker propranolol facilitated PGE2 synthesis. Acetylcholine did not affect PG biosynthesis. These results indicate that norepinephrine and epinephrine act on PG biosynthesis as adrenergic agonists in these cultured RGECs and that an alpha 1-receptor couples PGI2 and PGE2 synthesis.
Ueda
F
F
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Ideguchi
K
K
Taniguchi
N
N
Kimura
K
K
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D004837:Epinephrine / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011247:Pregnancy; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D011817:Rabbits; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D013270:Stomach / Q000166:cytology / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D011453:Prostaglandins; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D016718:Arachidonic Acid; D015016:Yohimbine; D015121:6-Ketoprostaglandin F1 alpha; D011433:Propranolol; D011464:Epoprostenol; D015232:Dinoprostone; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine; D010646:Phentolamine