Mizinga K M, Thompson F N, Stuedemann J A, Edwards G L
Department of Physiology and Pharmacology, University of Georgia, Athens 30602.
Drug Chem Toxicol. 1993;16(3):307-19. doi: 10.3109/01480549309081822.
To study the effect of endophyte (Acremonium coenophialum) on hypothalamic and striatal dopamine D2 receptors, male rats (n = 14/group) were pair-fed diets containing 50% Rat Chow and 50% either endophyte-infected (E+) or noninfected (E-) fescue (Festuca arundinacea Schreb.) seed for 21 days. Concentrations of ergovaline and saturated pyrrolizidines were 1.91 micrograms/g and 2.84 mg/g, respectively in E+, and undetectable in E- fescue seed. To monitor endophyte effects, rats were weighed weekly and serum derived from trunk blood (d 21) was analyzed for prolactin. Corpus striatum and hypothalamic tissue was assayed for dopamine D2 receptors using [3H]spiperone and [125I]epidepride, respectively. The endophyte depressed (P < .06) serum prolactin concentrations. Average daily gain during the study (21 d) was depressed (P < .0043) in rats fed E+ compared to controls. The endophyte increased (P < .03) striatal D2 receptor affinity (KD = 48.70 vs 54.95 pM) with no change (P > .28) in receptor density (Bmax = 25.59 vs 28.00 pmol/mg of tissue) in E+ and E- rats, respectively. Hypothalamic D2 receptor density (Bmax = 1.79 vs 1.57 pmol/mg of tissue) and affinity (KD = 17.5 vs 17.26 pM) were not (P > .66) different between E+ and E- rats, respectively. These data suggest changes in D2 receptor binding characteristics, particularly receptor affinity, may contribute to signs of fescue toxicosis.
为研究内生真菌(共生黑麦草内生真菌)对下丘脑和纹状体多巴胺D2受体的影响,将雄性大鼠(每组n = 14只)成对饲养,给予含50%大鼠饲料和50%感染内生真菌(E+)或未感染内生真菌(E-)的羊茅(高羊茅)种子的日粮,持续21天。E+羊茅种子中麦角缬氨酸和饱和吡咯里西啶的浓度分别为1.91微克/克和2.84毫克/克,E-羊茅种子中未检测到。为监测内生真菌的影响,每周称重大鼠体重,并分析来自躯干血(第21天)的血清中的催乳素。分别使用[3H]螺哌隆和[125I]表哌啶对纹状体和下丘脑组织中的多巴胺D2受体进行测定。内生真菌使血清催乳素浓度降低(P < 0.06)。与对照组相比,喂食E+的大鼠在研究期间(21天)的平均日增重降低(P < 0.0043)。内生真菌使纹状体D2受体亲和力增加(P < 0.03)(KD = 48.70对54.95皮摩尔),而E+和E-大鼠的受体密度(Bmax = 25.59对28.00皮摩尔/毫克组织)无变化(P > 0.28)。E+和E-大鼠下丘脑D2受体密度(Bmax = 1.79对1.57皮摩尔/毫克组织)和亲和力(KD = 17.5对17.26皮摩尔)分别无差异(P > 0.66)。这些数据表明D2受体结合特性的变化,特别是受体亲和力的变化,可能导致羊茅中毒症状。