Endothelin is a potent constrictor of the lamb ductus arteriosus

1989 ◽  
Vol 67 (8) ◽  
pp. 902-904 ◽  
Author(s):  
Flavio Coceani ◽  
Craig Armstrong ◽  
Lois Kelsey
Keyword(s):  
Contractile Response ◽  
Ductus Arteriosus ◽  
Extended Period ◽  
Cytochrome P 450

Endothelin was tested on isolated ductus arteriosus preparations from mature fetal Iambs. At low [Formula: see text] (18–24 Torr; 1 Torr = 133.3 Pa), the compound constricted the vessel dose-dependently over the range from about 10−10 to 10−7 M. The contraction was sustained and did not subside even after an extended period of washing. Endothelin was also effective on tissues ([Formula: see text], 217–231 Torr; indomethacin, 2.8 × 10−6 M) that had been completely relaxed with CO (CO/O2 ratio, 0.28). CO treatment interferes with a cytochrome P-450 mechanism, which is considered crucial for the contractile response of the vessel to oxygen. These findings are consistent with a role of endothelin in the closure of the ductus arteriosus at birth.Key words: ductus arteriosus closure, oxygen, cytochrome P-450.

scholarly journals Conversion of 19-oxo[2β-2H]androgens into oestrogens by human placental aromatase. An unexpected stereochemical outcome

1990 ◽  
Vol 268 (3) ◽  
pp. 553-561 ◽  
Author(s):  
P A Cole ◽  
C H Robinson
Keyword(s):  
Active Site ◽  
Extended Period ◽  
Direct Role ◽  
Methyl Group ◽  
Enzyme Active Site ◽  
Model Studies ◽  
The Third ◽  
Intensive Investigation ◽  
Cytochrome P 450

Aromatase is a cytochrome P-450 enzyme that catalyzes the conversion of androgens into oestrogens via sequential oxidations at the 19-methyl group. Despite intensive investigation, the mechanism of the third step, conversion of the 19-aldehydes into oestrogens, has remained unsolved. We have previously found that a pre-enolized 19-al derivative undergoes smooth aromatization in non-enzymic model studies, but the role of enolization by the enzyme in transformations of 19-oxoandrogens has not been previously investigated. The compounds 19-oxo[2 beta-2H]testosterone and 19-oxo[2 beta-2H]androstenedione have now been synthesized. Exposure of either of these compounds to microsomal aromatase, in the absence of NADPH, for an extended period led to no significant 2H loss or epimerization at C-2, leaving open the importance of an active-site base. However, in the presence of NADPH there was an unexpected substrate-dependent difference in the stereoselectivity of H loss at C-2 in the enzyme-induced aromatization of 19-oxo[2 beta-2H]-testosterone versus 19-oxo[2 beta-2H]androstenedione. The aromatization results for 17 beta-ol derivative 19-oxo[2 beta-2H]-testosterone correspond to about 1.2:1 2 beta-H/2 alpha-H loss from unlabelled 19-oxotestosterone. In contrast, aromatization results for 19-oxo[2 beta-2H]androstenedione correspond to at least 11:1 2 beta-H/2 alpha-H loss from unlabelled 19-oxoandrostenedione. This substrate-dependent stereoselectivity implies a direct role for an enzyme active-site base in 2-H removal. Furthermore, these results argue against the proposal that 2 beta-hydroxylation is the obligatory third step in aromatase action.

Endothelin-1 release from lamb ductus arteriosus; relevance to postnatal closure of the vessel

1991 ◽  
Vol 69 (2) ◽  
pp. 218-221 ◽  
Author(s):  
Flavio Coceani ◽  
Lois Kelsey
Keyword(s):  
Key Words ◽  
Conformational Change ◽  
Contractile Response ◽  
Ductus Arteriosus ◽  
Endothelin 1 ◽  
Wet Weight ◽  
Presence And Absence ◽  
Near Term ◽  
Cytochrome P 450 ◽  
Postnatal Closure

Our previous investigations have shown that endothelin-1 (ET-1) is a singularly potent constrictor of the ductus arteriosus and that a cytochrome P-450 system located in the sarcolemma is crucial for the contractile response of the vessel to oxygen. We have now studied the release of ET-1 from isolated ductus arteriosus preparations of near-term fetal lambs. Preparations produced measurable amounts of ET-1 under basal conditions (about 0.04 pg/100 mg wet weight∙min) both in the presence and absence of the endothelium. Anisomycin (10−4 M) reduced this release by 50%, while thrombin (1 U/mL) doubled the release. Treatment with a CO mixture (CO/O2 ratio, 0.27) inhibited ET-1 release from intact and endothelium-denuded preparations. We propose that oxygen triggers closure of the ductus arteriosus at birth by causing a conformational change in a specific cytochrome P-450, which, in turn, provides the signal for the synthesis of the constrictor ET-1.Key words: ductus arteriosus closure, oxygen, cytochrome P-450, endothelin.

Cytochrome P 450-linked monooxygenase: involvement in the lamb ductus arteriosus

1984 ◽  
Vol 246 (4) ◽  
pp. H640-H643 ◽  
Author(s):  
F. Coceani ◽  
N. C. Hamilton ◽  
J. Labuc ◽  
P. M. Olley
Keyword(s):  
Cytochrome P450 ◽  
Guinea Pig ◽  
Partial Pressure ◽  
Contractile Response ◽  
Muscle Tone ◽  
Ductus Arteriosus ◽  
Inhibitory Effect ◽  
Gas Mixture ◽  
O2 Partial Pressure ◽  
Cytochrome P 450

CO and metyrapone were tested on isolated ductus arteriosus preparations from mature fetal lambs equilibrated at low (4-12 Torr) and high (511-712 Torr) O2 partial pressure (PO2). CO completely reversed the contractile tension of the ductus at either PO2 value and was equally effective in the absence and presence of indomethacin. CO relaxation still occurred when the tissue was exposed to a gas mixture having a CO-to-O2 ratio of 0.27. The inhibitory effect of CO on the O2-contracted ductus was variably reversed by light. Metyrapone was also a relaxant agent, and its action was greater at low than at high PO2. Unlike the lamb ductus, the O2-constricted guinea pig ductus did not respond to CO (maximum CO-to-O2 ratio around 1), whereas it was relaxed by metyrapone. These findings implicate a cytochrome P450-catalyzed enzymic process in the maintenance of muscle tone of the lamb ductus arteriosus and in the contractile response of the vessel to O2.

Role of the exosporial membrane in attachment and germination of C. sporogenes

1993 ◽  
Vol 51 ◽  
pp. 38-39
Author(s):  
B.J. Panessa-Warren ◽  
G.T. Tortora ◽  
J.B. Warren
Keyword(s):  
Enzymatic Degradation ◽  
Light Transmission ◽  
Extended Period ◽  
Growth Conditions ◽  
Clostridium Sporogenes ◽  
Radiation Chemical ◽  
Physical Trauma ◽  
Extended Contact ◽  
Cold Pressure

Some bacteria are capable of forming highly resistant spores when environmental conditions are not adequate for growth. Depending on the genus and species of the bacterium, these endospores are resistant in varying degrees to heat, cold, pressure, enzymatic degradation, ionizing radiation, chemical sterilants,physical trauma and organic solvents. The genus Clostridium, responsible for botulism poisoning, tetanus, gas gangrene and diarrhea in man, produces endospores which are highly resistant. Although some sporocides can kill Clostridial spores, the spores require extended contact with a sporocidal agent to achieve spore death. In most clinical situations, this extended period of treatment is not possible nor practical. This investigation examines Clostridium sporogenes endospores by light, transmission and scanning electron microscopy under various dormant and growth conditions, cataloging each stage in the germination and outgrowth process, and analyzing the role played by the exosporial membrane in the attachment and germination of the spore.

scholarly journals Microfluidic tumor-on-a-chip model to evaluate the role of tumor environmental stress on NK cell exhaustion

2021 ◽  
Vol 7 (8) ◽  
pp. eabc2331 ◽  
Author(s):  
Jose M. Ayuso ◽  
Shujah Rehman ◽  
Maria Virumbrales-Munoz ◽  
Patrick H. McMinn ◽  
Peter Geiger ◽  
...  
Keyword(s):  
Nk Cells ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Waste Product ◽  
Extended Period ◽  
Cell Exhaustion

Solid tumors generate a suppressive environment that imposes an overwhelming burden on the immune system. Nutrient depletion, waste product accumulation, hypoxia, and pH acidification severely compromise the capacity of effector immune cells such as T and natural killer (NK) cells to destroy cancer cells. However, the specific molecular mechanisms driving immune suppression, as well as the capacity of immune cells to adapt to the suppressive environment, are not completely understood. Thus, here, we used an in vitro microfluidic tumor-on-a-chip platform to evaluate how NK cells respond to the tumor-induced suppressive environment. The results demonstrated that the suppressive environment created by the tumor gradually eroded NK cell cytotoxic capacity, leading to compromised NK cell surveillance and tumor tolerance. Further, NK cell exhaustion persisted for an extended period of time after removing NK cells from the microfluidic platform. Last, the addition of checkpoint inhibitors and immunomodulatory agents alleviated NK cell exhaustion.

scholarly journals Role of Cytochrome b5 in Hydroxylation by a Reconstituted Cytochrome P-450-containing System

1974 ◽  
Vol 249 (21) ◽  
pp. 6701-6709
Author(s):  
Anthony Y.H. Lu ◽  
Susan B. West ◽  
Mary Vore ◽  
Dene Ryan ◽  
Wayne Levin
Keyword(s):  
Cytochrome B5 ◽  
Cytochrome P 450

Toll-like receptors 2 and 4 exert opposite effects on the contractile response induced by serotonin in mouse colon: role of serotonin receptors

2016 ◽  
Vol 101 (8) ◽  
pp. 1064-1074 ◽  
Author(s):  
R. Forcén ◽  
E. Latorre ◽  
J. Pardo ◽  
A. I. Alcalde ◽  
M. D. Murillo ◽  
...  
Keyword(s):  
Serotonin Receptors ◽  
Contractile Response ◽  
Toll Like Receptors ◽  
Mouse Colon

scholarly journals Decrease in hepatic cytochrome P-450 by cobalt. Evidence for a role of cobalt protoporphyrin

1982 ◽  
Vol 204 (1) ◽  
pp. 103-109 ◽  
Author(s):  
J F Sinclair ◽  
P R Sinclair ◽  
J F Healey ◽  
E L Smith ◽  
H L Bonkowsky
Keyword(s):  
Chick Embryo ◽  
Gel Electrophoresis ◽  
Polyacrylamide Gel Electrophoresis ◽  
Polyacrylamide Gel ◽  
Cobalt Protoporphyrin ◽  
Cytochrome P 450 ◽  
Hepatic Cytochrome

Exposure of cultured chick-embryo hepatocytes to increasing concentrations of CoCl2 in the presence of allylisopropylacetamide results in formation of cobalt protoporphyrin, with a reciprocal decrease in haem and cytochrome P-450. Treatment of rats with CoCl2 (84 mumol/kg) and 5-aminolaevulinate (0.2 mmol/kg) also results in formation of cobalt protoporphyrin and a decrease in cytochrome P-450 in the liver. Hepatic microsomal fractions from rats treated with phenobarbital, CoCl2 and 5-aminolaevulinate were analysed by polyacrylamide gel electrophoresis. Cobalt protoporphyrin was associated mainly with proteins of 50000-53000 mol.wt. The results suggest that the formation of cobalt protoporphyrin occurred at the expense of the synthesis of haem, leading to a decrease in cytochrome P-450. Furthermore, the cobalt protoporphyrin that was formed may itself have been incorporated into apocytochrome P-450.

Sign in / Sign up

Export Citation Format

Share Document