Renin stimulates decidual prostaglandin production via a novel mechanism that is independent of angiotensin II formation.
Renin is a proteolytic enzyme that has been considered to have only one function which is to cleave angiotensinogen between the 10th and 11th amino acids to form angiotensin-1. This is then converted to angiotensin-II, a potent vasoconstrictor, antinatriuretic and antidiuretic by angiotensin-converting enzyme. We have investigated the action of renin to stimulate prostaglandin production by decidual cells and in so doing have generated data that challenge the prevailing dogma. Renin stimulates decidual prostaglandin production in a concentration-related fashion that is unaffected by saralasin treatment. This stimulatory action of renin is enhanced rather than reduced by arachidonic acid treatment but abolished by treatment with cycloheximide or actinomycin D. Renin caused a more rapid recovery of decidual prostaglandin biosynthesis from acetylsalicylic acid treatment than did control media. Moreover, renin treatment of both decidual and amnion cells induced increased levels of PGHS-2 within 2 h. Collectively, these results indicate that renin can act directly, separately from the generation of angiotensin-I and II. In this case renin can induce PGHS expression.
Mitchell
M D
MD
Department of Pharmacology and Clinical Pharmacology, University of Auckland, New Zealand.
Edwin
S S
SS
Pollard
J K
JK
Trautman
M S
MS
D000650:Amnion / Q000187:drug effects / Q000378:metabolism; D000804:Angiotensin II / Q000096:biosynthesis*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003656:Decidua / Q000187:drug effects / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011453:Prostaglandins / Q000096:biosynthesis*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012083:Renin / Q000494:pharmacology*; D012504:Saralasin / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D011453:Prostaglandins; D011500:Protein Synthesis Inhibitors; D000804:Angiotensin II; D003609:Dactinomycin; D016718:Arachidonic Acid; D003513:Cycloheximide; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin; D012504:Saralasin; D015232:Dinoprostone