Substance P (NK1) receptor immunoreactivity on endothelial cells of the rat tracheal mucosa.
Substance P released from sensory nerve fibers causes plasma leakage through an action on neurokinin-1 (NK1 or substance P) receptors. However, it is unknown whether the leakage results from a direct action of substance P on endothelial cells. We determined the distribution of NK1 receptors at sites of plasma leakage in the rat tracheal mucosa, using NK1 receptor-immunoreactive endosomes as markers of substance P-induced receptor internalization. We found that immunoreactive endosomes were located in the endothelial cells of venules and capillaries but not in those of arterioles. Five minutes after vagal stimulation for 1 min, the number of immunoreactive endosomes in endothelial cells was increased 5-fold in postcapillary venules (mean of 17.4 endosomes/100 micron2 compared with a baseline value of 3.4), 15-fold in collecting venules (12.1 compared with 0.8), and 4-fold in capillaries (2.5 compared with 0.7). No endosomes were found in arterioles under either condition. The number of immunoreactive endosomes in individual vessels corresponded to the amount of stimulus-induced plasma leakage. Both the receptor internalization and the plasma leakage were blocked by the selective NK1 receptor antagonist SR-140333 (100 microgram/kg iv). Although both substance P (5 microgram/kg iv) and platelet-activating factor (5 microgram/kg iv) caused plasma leakage, only substance P induced receptor internalization. We conclude that substance P, released from sensory nerve fibers, causes plasma leakage through a direct action on endothelial cells of venules, and that this action is followed by the internalization of NK1 receptors into endosomes.
Bowden
J J
JJ
Cardiovascular Research, University of California, San Francisco 94143, USA.
Baluk
P
P
Lefevre
P M
PM
Vigna
S R
SR
McDonald
D M
DM
D000818:Animals; D001160:Arterioles / Q000166:cytology; D015415:Biomarkers; D004558:Electric Stimulation; D004705:Endocytosis; D011992:Endosomes / Q000502:physiology / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D007150:Immunohistochemistry; D007249:Inflammation; D008297:Male; D009092:Mucous Membrane / Q000098:blood supply / Q000294:innervation; D051381:Rats; D011916:Rats, Inbred F344; D018040:Receptors, Neurokinin-1 / Q000032:analysis*; D013373:Substance P / Q000502:physiology; D014132:Trachea / Q000098:blood supply* / Q000294:innervation; D014630:Vagus Nerve / Q000502:physiology; D014699:Venules / Q000166:cytology
D015415:Biomarkers; D018040:Receptors, Neurokinin-1; D013373:Substance P