Substance P causes adhesion of neutrophils to endothelial cells via protein kinase C.
The sensory neuropeptide substance P is known to be involved in neurogenic inflammation. We examined the effect of substance P on neutrophil adhesion to human umbilical vein endothelial cells (HUVEC). Stimulation of HUVEC with substance P increased their adhesion to neutrophils in a time- and concentration (10(-10)-10(-7) M)-dependent manner. The adhesion was inhibited by the tachykinin NK1 receptor antagonist (+)-(2S,3S)-3-(2-Methoxybenzylamino)-2-phenylpiperidine (CP-99,994) and also by the protein kinase C inhibitors 1-(5-Isoquinolinesulfonyl)-2-methyl piperazine (H-7) and bisindolylmaleimide (BIM), but not by the protein kinase A inhibitor N-12-(p-Bromocinnamylamino) ethyl]-S-isoquinoline sulfonamide (H-89). These results indicate that substance P induces adhesion of neutrophils to HUVEC by activation of protein kinase C via the NK1 receptor on the HUVEC.
Tominaga
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
Honda
K
K
Akahoshi
A
A
Makino
Y
Y
Kawarabayashi
T
T
Takano
Y
Y
Kamiya
H
H
D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D064729:Neurokinin-1 Receptor Antagonists; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014469:Umbilical Arteries / Q000166:cytology / Q000187:drug effects
D004791:Enzyme Inhibitors; D064729:Neurokinin-1 Receptor Antagonists; D013373:Substance P; D011493:Protein Kinase C