Ductus arteriosus: involvement of a sarcolemmal cytochrome P-450 in O2 constriction?
Our previous studies implicate a cytochrome P-450-based mechanism in the constrictor response of the ductus arteriosus to oxygen. The present experiments were conducted on saponin-skinned strips of ductal muscle from mature fetal lambs to determine the location, sarcolemmal versus intracellular, of this cytochrome and to obtain a better insight into the sequence of events underlying the action of oxygen. Skinned preparations contracted to free Ca2+ over the range between 0.1 and 5-10 microM (pCa 7 to 5). In contrast, oxygen (PO2, 608-690 Torr; 1 Torr = 133.3 Pa) had no significant effect, both in the absence and presence of 10 microM calcium. Carbon monoxide, tested as pure CO or a CO-O2 mixture (ratio 0.28), did not relax preparations maximally contracted with calcium. These findings indicate that oxygen exerts its effect on the plasma membrane of ductus muscle cells and that a membrane-bound cytochrome P-450 mechanism likely functions as the signal transducer for oxygen in the formation of a constrictor agent.
Coceani
F
F
Research Institute, Hospital for Sick Children, Toronto, Ont., Canada.
Wright
J
J
Breen
C
C
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004373:Ductus Arteriosus / Q000201:enzymology*; D005260:Female; D005333:Fetus / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010100:Oxygen / Q000494:pharmacology*; D011247:Pregnancy; D012503:Saponins / Q000494:pharmacology; D012508:Sarcolemma / Q000201:enzymology*; D012756:Sheep
D012503:Saponins; D003577:Cytochrome P-450 Enzyme System; D010100:Oxygen