Vascular responses of human skin to injection of substance P and mechanism of action.
The mechanism of cutaneous inflammation caused by substance P in human skin was assessed in five subjects receiving i.d. injections (5-405 pmol) at pH 7.2 as compared to histamine (0.08-1.6 nmol), compound 48/80 (100 ng) and solvent control. Both substance P and histamine produced sigmoid dose-response curves for the following parameters: 1 min and 5 min planimetrically measured areas of erythema, and mean diameter of weal. Substance P pretreatment induced tachyphylaxis, as assessed by standard methods with adequate controls, to both histamine and to substance P and vice versa. Erythema following substance P i.d. was not blocked by a constricting band. Diphenhydramine, and to a lesser extent doxantrazole, (but not cimetidine or indomethacin) when assessed as inhibitors after oral pretreatment, did shift dose response curves for histamine and substance P to the right. Light and electron microscopic assessment of mast cells was compared in substance P and solvent control injected human skin. These results support a possible role for substance P in cutaneous inflammation acting either directly or via histamine release from mast cells.
D002927:Cimetidine / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008407:Mast Cells / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply* / Q000648:ultrastructure; D013373:Substance P / Q000494:pharmacology*; D013892:Thioxanthenes / Q000494:pharmacology; D044004:Xanthones
D011453:Prostaglandins; D013892:Thioxanthenes; D044004:Xanthones; D013373:Substance P; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine; C010134:doxantrazole; D007213:Indomethacin