Patrini G, Massi P, Rubino T, Donin L, Gori E, Parolaro D
Institute of Pharmacology, Faculty of Sciences, University of Milan, Italy.
Eur J Pharmacol. 1992 Jan 21;210(3):259-64. doi: 10.1016/0014-2999(92)90413-x.
The effect of intracerebroventricularly (i.c.v.) administered histamine (100 micrograms/rat) on intestinal myoelectrical activity was investigated in the jejunum of fasted rats. Histamine caused the disappearance of phase III and a partial reduction of phase II of migrating myoelectric complexes. This effect was antagonized by i.c.v. pretreatment with mepyramine (10 micrograms/rat), an H1 receptor antagonist. Lesions of central noradrenergic neurons by i.c.v. injection of the neurotoxin 6-hydroxydopamine strongly reduced both the inhibition of intestinal propulsion and the migrating myoelectric complexes profile induced by i.c.v. histamine, whereas pretreatment with p-chlorophenylalanine, a selective depletor of serotonin stores, had no effect. It thus appears that aminergic pathways are involved in the visceral effects of central histamine. Mepyramine (200 micrograms/rat i.c.v.) partially reduced the slowing of intestinal transit induced by high doses of morphine. Pretreatment with compound 48/80 (10 micrograms/rat i.c.v.), a mast cell degranulator, but not with alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, reduced the antipropulsive action of i.c.v. morphine to the same extent as mepyramine, suggesting that histamine released from cerebral mast cells by high doses of morphine could contribute to the intestinal inhibition by morphine.
研究了脑室内（i.c.v.）注射组胺（100微克/大鼠）对禁食大鼠空肠肠肌电活动的影响。组胺导致移行性肌电复合波的III期消失和II期部分减弱。这种作用被H1受体拮抗剂美吡拉敏（10微克/大鼠）i.c.v.预处理所拮抗。通过i.c.v.注射神经毒素6-羟基多巴胺对中枢去甲肾上腺素能神经元造成损伤，可强烈降低i.c.v.组胺诱导的肠推进抑制和移行性肌电复合波变化，而用对氯苯丙氨酸（一种血清素储存的选择性耗竭剂）预处理则无作用。因此，胺能通路似乎参与了中枢组胺的内脏效应。美吡拉敏（200微克/大鼠i.c.v.）部分减轻了高剂量吗啡诱导的肠转运减慢。用肥大细胞脱颗粒剂化合物48/80（10微克/大鼠i.c.v.）预处理，但不用组氨酸脱羧酶不可逆抑制剂α-氟甲基组氨酸预处理，可将i.c.v.吗啡的抗推进作用减轻至与美吡拉敏相同的程度，这表明高剂量吗啡从脑肥大细胞释放的组胺可能有助于吗啡对肠道的抑制作用。
