Cross J M, Mercer D W, Gunter J, Miller T A
Department of Surgery, University of Texas-Houston Medical School, Houston, Tex, USA.
J Gastrointest Surg. 1997 May-Jun;1(3):257-65; discussion 265. doi: 10.1016/s1091-255x(97)80118-7.
Dopamine and cholecystokinin have been colocalized in neurons and represent endogenous enteric neurotransmitters. Both peptides possess potent protective actions against gastric injury when given exogenously. This study was undertaken in conscious female rats to test the hypothesis that cholecystokinin may exert its protective actions via release of dopamine. Experiments were designed to ascertain whether L-dopa, a dopamine precursor, could prevent gastric injury with the same degree of efficacy as cholecystokinin and to determine what role alpha-2 adrenoreceptors and dopamine receptors play in mediating the protective actions of these peptides. Intraperitoneal administration of L-dopa (1 to 25 mg/kg) in a dose-dependent manner prevented the type of macroscopic injury to the acid-secreting portion of the stomach that is caused by 1 ml of orogastric acidified ethanol (150 mmol/L hydrochloric acid/50% ethanol), an effect corroborated by histologic examination. Administration of either the alpha-2 adreno-receptor antagonist yohimbine (0.1 to 1.0 mg/kg) or the dopamine receptor antagonist haloperidol (1 to 5 mg/kg) caused a partial reversal of L-dopa-induced protection but not the protective actions of subcutaneous cholecystokinin (100 microg/kg). Simultaneous administration of both receptor antagonists had an additive effect and completely reversed the protective actions of L-dopa. The dopamine precursor L-dopa was just as effective in maintaining the integrity of the gastric epithelium in the face of a damaging insult as the gut peptide cholecystokinin. However, the data indicate that L-dopa initiates its protective actions through activation of both alpha-2 adrenoreceptors and dopamine receptors, whereas the protective effects of cholecystokinin are elicited by means of a different mechanism.
多巴胺和胆囊收缩素已在神经元中共定位，并代表内源性肠神经递质。这两种肽在外源性给予时都对胃损伤具有强大的保护作用。本研究在清醒的雌性大鼠中进行，以检验胆囊收缩素可能通过释放多巴胺发挥其保护作用的假说。实验旨在确定多巴胺前体L-多巴是否能以与胆囊收缩素相同的疗效预防胃损伤，并确定α-2肾上腺素能受体和多巴胺受体在介导这些肽的保护作用中所起的作用。以剂量依赖性方式腹腔注射L-多巴（1至25mg/kg）可预防由1ml经口胃内酸化乙醇（150mmol/L盐酸/50%乙醇）引起的胃泌酸部分的宏观损伤类型，组织学检查证实了这一效果。给予α-2肾上腺素能受体拮抗剂育亨宾（0.1至1.0mg/kg）或多巴胺受体拮抗剂氟哌啶醇（1至5mg/kg）会使L-多巴诱导的保护作用部分逆转，但不会使皮下注射胆囊收缩素（100μg/kg）的保护作用逆转。同时给予两种受体拮抗剂具有相加作用，并完全逆转了L-多巴的保护作用。多巴胺前体L-多巴在面对损伤性刺激时维持胃上皮完整性方面与肠肽胆囊收缩素同样有效。然而，数据表明L-多巴通过激活α-2肾上腺素能受体和多巴胺受体启动其保护作用，而胆囊收缩素的保护作用则通过不同机制引发。
