Douglas A J, Dye S, Leng G, Russell J A, Bicknell R J
Department of Physiology, University Medical School, Edinburgh, UK.
J Neuroendocrinol. 1993 Jun;5(3):307-14. doi: 10.1111/j.1365-2826.1993.tb00487.x.
We have investigated the influence of endogenous opioids on oxytocin secretion during pregnancy. In blood-sampled conscious rats on days 18 and 21 of pregnancy plasma oxytocin concentration, measured by radioimmunoassay, was significantly increased compared to non-pregnant or post-partum rats. On days 15, 18 and 21 of pregnancy but not in non-pregnant, early pregnant or post-partum rats, the opioid antagonist naloxone caused a significant increase in plasma oxytocin compared to vehicle injection, indicating activation of an endogenous opioid restraint over oxytocin secretion. Electrically stimulated neural lobes isolated from 16- and 21-day pregnant rats released more oxytocin than those from non-pregnant rats. However, naloxone (10(-5) M) was less effective at potentiating, and the kappa-opioid agonist U50,488 (10(-5)M) was less effective at inhibiting, stimulated release at the end of pregnancy than in non-pregnant rats suggesting desensitization of oxytocin nerve terminals to actions of endogenous opioids. Neural lobes from male rats drinking 2% saline for 4 days also showed desensitization of oxytocin nerve endings to naloxone. Neither neural lobe content of dynorphin A(1-8), an endogenous kappa-opioid, nor prodynorphin mRNA expression, measured by in situ hybridization histochemistry in the supraoptic nucleus altered during pregnancy. However, neural lobe content of Met5-enkephalin significantly decreased by day 21 of gestation suggesting enhanced release.(ABSTRACT TRUNCATED AT 250 WORDS)
我们研究了内源性阿片类物质对孕期催产素分泌的影响。在妊娠第18天和第21天采集血样的清醒大鼠中，通过放射免疫测定法测得的血浆催产素浓度与未孕或产后大鼠相比显著升高。在妊娠第15、18和21天，但在未孕、早孕或产后大鼠中未出现这种情况，与注射赋形剂相比，阿片类拮抗剂纳洛酮使血浆催产素显著增加，表明内源性阿片类物质对催产素分泌的抑制作用被激活。从妊娠16天和21天的大鼠分离出的神经垂体经电刺激后释放的催产素比未孕大鼠的更多。然而，与未孕大鼠相比，在妊娠末期，纳洛酮（10⁻⁵ M）增强催产素释放的效果较差。κ-阿片类激动剂U50,488（10⁻⁵ M）抑制催产素释放的效果也较差，提示催产素神经末梢对内源性阿片类物质的作用发生了脱敏。饮用2%盐水4天的雄性大鼠的神经垂体也显示出催产素神经末梢对纳洛酮的脱敏。通过原位杂交组织化学法测定，视上核中内源性κ-阿片类物质强啡肽A(1-8)的神经垂体含量以及前强啡肽mRNA表达在孕期均未改变。然而，在妊娠第21天时，甲硫氨酸脑啡肽的神经垂体含量显著下降，提示其释放增加。（摘要截短至250字）
