Possible Interaction: Ethanol and Bradykinin

“Finally, we demonstrated that the IL-1-… of PGE2 release in response to BK was reduced by … presence of ethanol in the culture medium, suggesting that part of the synergistic action of IL-1 and … on prostanoid production was dependent on the activation of the PC-specific PLD pathway.”

“Priming of synovial cells with rIL-1 beta 24 h before exposure to BK in the presence of ethanol further enhanced the BK-induced formation of PEt.”

“The observation that ethanol could significantly reduce [3H]PtdOH formation in myoblasts stimulated with BK and thrombin indicates that stimulation of PLD has a major role.”

“Agonists such as bradykinin , histamine, vasopressin, alpha-thrombin, and adenosine triphosphate (ATP) stimulated up to 15-fold accumulation of phosphatidylethanol (PEt) in the presence of ethanol through PLD-catalyzed phosphatidyltransferase activity.”

“Acute exposure to ethanol resulted in an inhibition of bradykinin mediated [Ca2+]i mobilization with significant effects observed only at 400 mM ethanol.”

“In addition, chronic ethanol exposure appears to have selective effects on receptor mediated [Ca2+]i mobilization because this response to bradykinin , but not neurotensin, was significantly reduced in cells exposed to ethanol.”

“Similarly, resting [Ca2+]i (64 +/- 2 nM) was unaffected by either chronic or acute ethanol as high as 400 mM. However, chronic exposure to ethanol significantly reduced the magnitude of bradykinin mediated [Ca2+]i mobilization both in the absence and presence of extracellular [Ca2+].”

“Chronic exposure of endothelial cells to ethanol (100 mmol/L) for 96 hours significantly increased bradykinin- , adenosine 5'-triphosphate-, and ionomycin-stimulated nitric oxide synthase activity without affecting basal enzyme activity.”

“The production of phosphatidic acid and choline suggests that bradykinin was increasing the activity of phospholipase …. Transphosphatidylation is a unique property of phospholipase D. In cells labeled with [3H]palmitic acid, bradykinin stimulated the transfer of … groups to both ethanol and propanol to form [3H]… and [3H]phosphatidylpropanol, respectively.”

“Acute exposure to ethanol over a range of 50 to 200 mM inhibited the stimulation of [3H]inositol phosphate formation elicited by neurotensin and bradykinin.”

“These data suggest that chronic ingestion of ethanol causes elevated blood pressure and augments the endothelium-dependent relaxation to bradykinin.”

“ Ethanol at 50 mM resembled mepacrine (46 microM) in that prostanoid release in response to bradykinin and A23187 was highly significantly reduced with little effect on release induced by arachidonic acid.”

“However, in cells cultivated for … days in 100 mM ethanol , PIP2 hydrolysis and IP1, IP2 and IP3 formation … stimulation by 10(-6)-10(-5) M bradykinin was markedly inhibited while there was no effect on the basal levels … on the levels found after stimulation with low concentrations of bradykinin.”