Parolaro D, Patrini G, Massi P, Mainardi P, Giagnoni G, Sala M, Gori E
Institute of Pharmacology, Faculty of Sciences, University of Milan, Italy.
J Pharmacol Exp Ther. 1989 Apr;249(1):324-8.
Histamine (HA) injected i.c.v. to rats inhibited intestinal propulsion in linear relation to the log of the administered doses (in the range from 20-100 micrograms/rat). In the same dose range HA also induced a dose-related analgesic effect (tail-flick test). The dose of HA maximally active by the i.c.v. route (100 micrograms/rat) showed neither of these effects when injected i.v. or i.p. HA-induced intestinal inhibition and analgesia were antagonized competitively by i.c.v. mepyramine (10 micrograms/rat), an H1 receptor antagonist, whereas cimetidine (10 micrograms/rat), an H2 receptor antagonist, had no effect. Repeated i.c.v. injections of HA resulted in tachyphylaxis of both intestinal inhibition and analgesia. Pretreatment with i.c.v. naloxone (20 micrograms/rat) antagonized the antipropulsive effect of HA in a noncompetitive fashion, but did not affect its antinociceptive action. The relevance of the central histaminergic system in the modulation of gastrointestinal motility and its relationship with the opioid system are discussed.
向大鼠脑室内注射组胺（HA）可抑制肠道推进，抑制程度与给药剂量的对数呈线性关系（剂量范围为20 - 100微克/大鼠）。在相同剂量范围内，HA还可诱导剂量相关的镇痛作用（甩尾试验）。脑室内注射途径的最大活性剂量（100微克/大鼠）的HA，静脉注射或腹腔注射时均未显示出这些作用。HA诱导的肠道抑制和镇痛作用可被脑室内注射的H1受体拮抗剂美吡拉敏（10微克/大鼠）竞争性拮抗，而H2受体拮抗剂西咪替丁（10微克/大鼠）则无作用。重复脑室内注射HA会导致肠道抑制和镇痛作用的快速耐受性。脑室内注射纳洛酮（20微克/大鼠）预处理以非竞争性方式拮抗HA的抗推进作用，但不影响其抗伤害感受作用。文中讨论了中枢组胺能系统在调节胃肠动力中的相关性及其与阿片系统的关系。
