Itch-associated response induced by intradermal serotonin through 5-HT2 receptors in mice.
Serotonin (5-HT) is pruritogenic in humans and suggested to be involved in some pruritic diseases. Our experiments were carried out to determine whether an intradermal injection of 5-HT would elicit itch-associated response in mice and to elucidate the 5-HT receptor subtypes involved in this 5-HT action. 5-HT (14.1-235 nmol site(-1)) injected intradermally into the rostral back elicited scratching of the injected site, with bell-shaped dose-response relationship. The scratching induced by 5-HT (100 nmol site(-1), peak effective dose) was suppressed by capsaicin (repeated administration) and the opioid antagonist naloxone, features being similar to human itching. Scratching was also elicited by the 5-HT2 receptor agonist alpha-methylserotonin, but not by the 5-HT1A receptor agonist R(+)-8-hydroxy-N,N-dipropyl-2-aminotetralin nor the 5-HT3 receptor agonists 2-methylserotonin and 1-phenylbiganide. Scratching induced by 5-HT and alpha-methylserotonin was inhibited by peroral pretreatment with 5-HT1/2 receptor antagonists methysergide and cyproheptadine. 5-HT-induced scratching was also inhibited by intradermal injection of methysergide. Peroral pretreatment with 5-HT3 receptor antagonists ondansetron and 3-tropanyl-3, 5-dichrobenzoate did not significantly suppress 5-HT-induced scratching. The results suggest that scratching induced by intradermal injection of 5-HT is itch-associated response. The 5-HT action may be mediated at least partly by cutaneous 5-HT2 receptors.
Yamaguchi
T
T
Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Nagasawa
T
T
Satoh
M
M
Kuraishi
Y
Y
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000008:administration & dosage; D007271:Injections, Intradermal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011537:Pruritus / Q000139:chemically induced*; D011930:Reaction Time / Q000187:drug effects; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000008:administration & dosage*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D009292:Narcotic Antagonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D009270:Naloxone; D006632:Histamine; D002211:Capsaicin