Roles of mast cells and sensory nerves in cutaneous vascular hyperpermeability and scratching behavior induced by poly-L-arginine in rats.
We investigated whether the polycation poly-L-arginine elicited cutaneous vascular hyperpermeability and scratching behavior and, if so, whether these responses involved mast cells and sensory nerves in rats. Intradermal injections of poly-L-arginine induced vascular hyperpermeability and scratching behavior. Combined treatment with chlorpheniramine and methysergide almost completely suppressed the poly-L-arginine (50 microg/site)-induced plasma leakage. Capsaicin desensitization and the tachykinin NK(1) receptor antagonist LY303870, (R)-1-[N-(2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino]propane, partially inhibited the leakage. In mast cell-deficient rats, poly-L-arginine only minimally induced plasma leakage. On the other hand, capsaicin desensitization and LY303870, but not chlorpheniramine or methysergide, suppressed the poly-L-arginine (200 microg/site)-induced scratching. Moreover, poly-L-arginine elicited the scratching even in mast cell-deficient rats. These results suggest that substance P is at least partly involved in both the cutaneous plasma leakage and the scratching behavior induced by poly-L-arginine. Moreover, mast cell-derived amines are suggested to be involved in the plasma extravasation but scarcely, if any, in the scratching behavior.
Hayashi
K
K
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, 411-8731, Shizuoka, Japan.
Sato
H
H
Kaise
T
T
Ohmori
K
K
Ishii
A
A
Sano
J
J
Karasawa
A
A
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D002744:Chlorpheniramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006020:Glycopeptides / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007271:Injections, Intradermal; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D008784:Methysergide / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D012867:Skin / Q000098:blood supply; D013373:Substance P / Q000494:pharmacology
C096759:1-(N-(2-methoxybenzyl)acetylamino)-3-(1H-indol-3-yl)-2-(N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino)propane; D006020:Glycopeptides; D006634:Histamine H1 Antagonists; D007211:Indoles; D010455:Peptides; D010880:Piperidines; D012702:Serotonin Antagonists; C015462:polyarginine; D012701:Serotonin; D013373:Substance P; D002744:Chlorpheniramine; D006632:Histamine; D002211:Capsaicin; C008890:phosphoramidon; D008784:Methysergide