Kavanagh G M, Sabroe R A, Greaves M W, Archer C B
Department of Dermatology, University of Bristol, Bristol Royal Infirmary, U.K.
Br J Dermatol. 1998 Apr;138(4):622-6. doi: 10.1046/j.1365-2133.1998.02172.x.
We have investigated the possible existence of the H3 histamine receptor in human skin with the highly selective ligands R alpha methylhistamine (RAMHA) (H3 agonist) and thioperamide (H3 antagonist). We compared the intradermal effects of RAMHA with histamine, and studied their potential modulation by the H1 antagonist terfenadine, and H2 antagonist cimetidine. The effects of RAMHA and thioperamide on codeine phosphate-, substance P- and histamine-induced weal and flare responses were also studied. RAMHA produced dose-related weal and flare responses that were approximately 10- and fivefold less, respectively, than responses to histamine. Flare responses to RAMHA were significantly inhibited by oral terfenadine (P < 0.05). Weal and flare responses to histamine after oral cimetidine showed much intersubject variation, and cimetidine did not significantly alter either RAMHA- or histamine-induced weal and flare responses. Codeine phosphate-, substance P- and histamine-induced responses were not significantly affected by concurrent administration of RAMHA. Thioperamide was not found to influence codeine phosphate-, substance P-, RAMHA- or histamine-induced effects. RAMHA induces vascular (weal and flare) responses in human skin, and these responses are partially inhibited by terfenadine. There is a trend for RAMHA to have an additive effect to the weal induced by substance P and histamine, although our results largely do not reach statistical significance. Thioperamide does not affect the vascular responses to RAMHA, codeine phosphate, histamine or substance P. We cannot conclude that the effects of RAMHA are induced by H3 receptors on cutaneous endothelial or mast cells.
我们使用高选择性配体Rα-甲基组胺（RAMHA）（H3激动剂）和硫代哌酰胺（H3拮抗剂）研究了人皮肤中H3组胺受体的可能存在情况。我们比较了RAMHA与组胺的皮内效应，并研究了H1拮抗剂特非那定和H2拮抗剂西咪替丁对它们的潜在调节作用。还研究了RAMHA和硫代哌酰胺对磷酸可待因、P物质和组胺诱导的风团及潮红反应的影响。RAMHA产生了与剂量相关的风团及潮红反应，分别比组胺引起的反应小约10倍和5倍。口服特非那定可显著抑制对RAMHA的潮红反应（P < 0.05）。口服西咪替丁后对组胺的风团及潮红反应在个体间差异很大，且西咪替丁未显著改变RAMHA或组胺诱导的风团及潮红反应。同时给予RAMHA对磷酸可待因、P物质和组胺诱导的反应没有显著影响。未发现硫代哌酰胺影响磷酸可待因、P物质、RAMHA或组胺诱导的效应。RAMHA可诱导人皮肤中的血管（风团及潮红）反应，且这些反应可被特非那定部分抑制。尽管我们的结果大多未达到统计学显著性，但RAMHA对P物质和组胺诱导的风团有产生相加效应的趋势。硫代哌酰胺不影响对RAMHA、磷酸可待因、组胺或P物质的血管反应。我们不能得出RAMHA的效应是由皮肤内皮细胞或肥大细胞上的H3受体诱导的结论。
