Substance P induction of itch-associated response mediated by cutaneous NK1 tachykinin receptors in mice.
Our experiments were conducted to determine whether substance P (SP) would elicit an itch sensation mediated by mast cells in mice. An intradermal injection of SP (10-135 microgram site-1) into the rostral back of the ICR mouse dose-dependently produced scratching of the injected site. The SP- (135 microgram site-1 = 100 nmol site-1) induced scratching was inhibited by capsaicin (repeated administration) and naloxone; features being similar to itch in humans. SP elicited scratching in mast cell-deficient (WBB6F1 W/Wv) mice as well as control (+/+) mice. Pretreatment with compound 48/80 produced similar degrees of inhibition of SP-induced scratching in mast cell-deficient mice as well as control +/+ and ICR mice. Intradermal injections of the NK1 receptor agonist GR73632 produced dose-dependent scratching, while the NK2 agonist GR64349 and the NK3 agonist senktide were without effects. SP-induced scratching was inhibited by the NK1 receptor antagonists spantide and L-668,169, but not by the NK2 antagonist L-659,877. The results suggest that scratching of the mouse induced by an i.d. injection of SP is itch-associated response. The SP action may be mediated at least partly by cutaneous NK1 receptors, and mast cells may not be key factors in SP-induced itching.
Andoh
T
T
Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Research Institute for Wakan-yaku, Toyama Medical & Pharmaceutical University, Toyama, Japan.
Nagasawa
T
T
Satoh
M
M
Kuraishi
Y
Y
D000818:Animals; D008297:Male; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D011537:Pruritus / Q000139:chemically induced*; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D018040:Receptors, Neurokinin-1; D013373:Substance P; D009270:Naloxone; D003189:p-Methoxy-N-methylphenethylamine; D009020:Morphine