Inhibitors of cytochrome P-450 reduce cyclic GMP stimulation by glyceryl trinitrate in LLC-PK1 kidney epithelial cells

1990 ◽  
Vol 342 (5) ◽  
Author(s):  
Henning Schr�der ◽  
Karsten Schr�r
Keyword(s):  
Epithelial Cells ◽  
Glyceryl Trinitrate ◽  
Cyclic Gmp ◽  
Kidney Epithelial Cells ◽  
Cytochrome P 450

Inhibition of nitrovasodilator- and acetylcholine-induced relaxation and cyclic GMP accumulation by the cytochrome P-450 substrate, 7-ethoxyresorufin

1992 ◽  
Vol 70 (9) ◽  
pp. 1297-1303 ◽  
Author(s):  
Brian M. Bennett ◽  
Bernard J. McDonald ◽  
Rita Nigam ◽  
Patrick G. Long ◽  
W. Craig Simon
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Cyclic Gmp ◽  
Guanylyl Cyclase ◽  
Competitive Inhibition ◽  
Direct Interaction ◽  
Inhibitory Effect ◽  
Rat Aorta ◽  
Endothelial Nitric Oxide ◽  
Cytochrome P 450

We examined the effect of the cytochrome P-450 substrate, 7-ethoxyresorufin (7-ER), and its corresponding product, resorufin, on nitrovasodilator- and endothelium-dependent relaxation of isolated rat aorta. The EC50 value for glyceryl trinitrate (GTN) induced relaxation was increased over 100-fold by 7-ER and less than 3-fold by resorufin. The EC50 value for sodium nitroprusside (SNP) induced relaxation was increased approximately 12-fold by 7-ER, acetylcholine (ACh) induced relaxation was abolished, and relaxation induced by isopropylnorepinephrine was not significantly affected. GTN-, SNP-, and ACh-induced increases in cyclic GMP accumulation were inhibited by 7-ER, as were basal cyclic GMP levels in endothelium-intact, but not endothelium-denuded tissues. 7-ER decreased GTN biotransformation in intact aorta and decreased the regioselective formation of glyceryl-1,2-dinitrate. The activation by GTN and SNP of aortic guanylyl cyclase in broken cell preparations was not affected by 7-ER, indicating that the inhibitory effect of 7-ER is probably not due to a direct interaction with guanylyl cyclase. The inhibitory effect of 7-ER on GTN-induced relaxation was not altered by the addition of superoxide dismutase, suggesting that 7-ER does not act by increasing superoxide anion concentration (which would serve to increase the degradation of nitric oxide (NO) formed during vascular GTN biotransformation). Our data provide further evidence for the role of the cytochrome P-450 – cytochrome P-450 reductase system in the biotransformation of GTN to an activator (presumably nitric oxide) of guanylyl cyclase. The data are consistent with a mode of action of 7-ER involving either competitive inhibition of vascular cytochrome P-450 or uncoupling of vascular cytochrome P-450 reductase from cytochrome P-450. The data also suggest that the cytochrome P-450 system facilitates NO release from SNP and that 7-ER has an inhibitory effect on endothelial nitric oxide synthase.Key words: glyceryl trinitrate, nitrovasodilators, cytochrome P-450, vascular smooth muscle, 7-ethoxyresorufin, endothelium, cyclic GMP.

Aberrant responses to growth-regulatory signals by variant kidney epithelial cells

1988 ◽  
Vol 254 (5) ◽  
pp. F747-F753
Author(s):  
M. M. Walsh-Reitz ◽  
R. I. Feldman ◽  
F. G. Toback
Keyword(s):  
Epithelial Cells ◽  
Growth Regulation ◽  
Growth Inhibitor ◽  
Soft Agar ◽  
Isoenzyme Analysis ◽  
Variant Cell ◽  
Kidney Epithelial Cells ◽  
Potent Growth ◽  
Potent Growth Inhibitor ◽  
Low K

Cultures that achieved a higher cell density than expected were noted during study of growth regulation in monkey kidney epithelial cells of the BSC-1 line. Multiplication of the variant cells was accelerated, compared with parental cells, as the cultures approached confluence. Cytogenetic analysis, immunofluorescence antibody reactions with specific monkey serum, isoenzyme analysis, microbiological studies, and lack of growth in soft agar indicated that the variant cells were not a contaminating cell type, lacked new isoenzymes, were free of microbial contamination, and were not transformed. Confluent variant cultures did not respond to a purified growth inhibitor protein produced by BSC-1 cells that inhibits multiplication and reduces cell Na content in subconfluent variant and parental cells. Vasopressin, which is a mitogen for parental cells, was a potent growth inhibitor for confluent cultures of variant cells. Low-K or high-Na media, which stimulate proliferation of parental cells, had no effect on growth of the variant cell line. These results suggest that enhanced multiplication of the variant cells is mediated by altered signal transduction pathways and/or receptors for growth-regulatory molecules.

Studies of the Effect of Glyceryl Trinitrate and Cyclic GMP on Calcium Turnover in Bovine Mesenteric Artery

1990 ◽  
Vol 66 (4) ◽  
pp. 277-282 ◽  
Author(s):  
Johan Ahlner ◽  
Krister L. Axelsson ◽  
Peter Karczewski ◽  
Rolf G. G. Andersson
Keyword(s):  
Glyceryl Trinitrate ◽  
Cyclic Gmp ◽  
Mesenteric Artery
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