Permeability of muscle capillaries to small heme-peptides. Evidence for the existence of patent transendothelial channels.
Two heme-peptides (HP) of about 20-A diameter (heme-undecapeptide [H11P], mol wt approximately 1900 and heme-octapeptide [H8P], mol wt approximately 1550), obtained by enzymic hydrolysis of cytochrome c, were sued as probe molecules in muscle capillaries (rat diaphragm). They were localized in situ by a perixidase reaction, enhanced by the addition of imidazole to the incubation medium. Chromatography of plasma samples showed that HPs circulate predominantly as monomers for the duration of the experiments and are bound by aldehyde fixatives to plasma proteins to the extent of approximately 50% (H8P) to approximately 95% (H11P). Both tracers cross the endothelium primarily via plasmalemmal vesicles which become progressively labeled (by reaction product) from the blood front to the tissue front of the endothelium, in three successive resolvable phases. By the end of each phase the extent of labeling reaches greater than 90% of the corresponding vesicle population. Labeled vesicles appear as either isolated units or chains which form patent channels across the endothelium. The patency of these channels was checked by specimen tilting and graphic analysis of their images. No evidence was found for early or preferential marking of the intercellular junctions and spaces by reaction product. It is concluded that the channels are the most likely candidate for structural equivalents of the small pores of the capillary wall since they are continuous, water-filled passages, and are provided with one or more strictures of less than 100 A. Their frequency remains to be established by future work.
D000818:Animals; D002196:Capillaries / Q000378:metabolism* / Q000648:ultrastructure; D002199:Capillary Permeability; D003574:Cytochrome c Group / Q000378:metabolism; D003964:Diaphragm; D006418:Heme / Q000097:blood / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008854:Microscopy, Electron; D009130:Muscle, Smooth / Q000098:blood supply* / Q000648:ultrastructure; D009842:Oligopeptides / Q000097:blood / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D013329:Structure-Activity Relationship
D003574:Cytochrome c Group; D009842:Oligopeptides; D006418:Heme