Chaud M, Franchi A M, Gimeno M F, Gimeno A L
Centro de Estudios Farmacológicos, Principios Naturales (CEFAPRIN), Buenos Aires, Argentina.
Prostaglandins. 1988 Jan;35(1):95-106. doi: 10.1016/0090-6980(88)90277-8.
The effects of gamma-linolenic acid (GLA) on the time-dependent constancy of spontaneous contractions (isometric developed tension = IDT and frequency of contractions = FC) in uterine strips isolated from spayed rats, were explored. Moreover, the influence of the unsaturated fatty acid on the basal generation and release of tissue prostaglandins (PGs) as well as the conversion of labelled GLA into prostanoids by the uterine tissue and the effects of p-bromo-phenacyl-bromide (BPB), were also studied. GLA (10(-7)M), attenuated significantly the spontaneous decrement of contractile constancy exhibited by control preparations during a period of 180 min of activity in isolation, whereas BPB (10(5) M) resulted in an augmented and faster decrement of inotropic constancy. Spontaneous changes in the constancy of uterine motility as time progressed involved similarly both IDT and FC. After 180 min of activity in isolation a basal generation and release of PGs E and F of the series 1 and 2, were detected. The challenge with 10(-7) M GLA (delivered immediately after isolation) enhanced significantly the output of PGE1 but did not influence the generation and release of PGE2 or PGF2 alpha. BPB (10(-5) M) had no significant effect on the basal output of PGE1, PGE2 or PGF2 but completely prevented the enhancing action of GLA on the synthesis and release of PGE1. Labelled GLA was mainly converted to PGE1 by rat uterine segments and negligible counts in the 2-series of prostanoids, were observed. In presence of BPB (10(-5) M) the conversion of 1-14C-GLA, to PGE1 was almost completely abolished. The foregoing evidences suggest that exogenous GLA is metabolized by the spayed rat uterus via an elongase, forming di-homogamma-linolenic acid (DHLA), which in turn is substrate for cyclo-oxygenase peroxidase reactions yielding finally PGE1. No evidence of a delta 5-desaturase activity, converting DHLA into arachidonate and further derivatives, was detected. Coincidently, exogenous GLA was able to support a better contractile constancy as a function of time than that evidenced in untreated uterine strips isolated from castrated rats.
研究了γ-亚麻酸（GLA）对从切除卵巢大鼠分离的子宫条带中自发收缩的时间依赖性稳定性（等长收缩张力=IDT和收缩频率=FC）的影响。此外，还研究了这种不饱和脂肪酸对组织前列腺素（PGs）的基础生成和释放的影响，以及子宫组织将标记的GLA转化为前列腺素的情况，以及对溴苯甲酰溴（BPB）的作用。GLA（10^(-7)M）显著减弱了对照制剂在180分钟的离体活动期间表现出的收缩稳定性的自发下降，而BPB（10^(-5)M）导致收缩力稳定性增强且下降更快。随着时间的推移，子宫运动稳定性的自发变化同样涉及IDT和FC。在离体活动180分钟后，检测到了1系列和2系列PGs E和F的基础生成和释放。用10^(-7)M GLA（在分离后立即给予）刺激显著增加了PGE1的产量，但不影响PGE2或PGF2α的生成和释放。BPB（10^(-5)M）对PGE1、PGE2或PGF的基础产量没有显著影响，但完全阻止了GLA对PGE1合成和释放的增强作用。标记的GLA主要被大鼠子宫段转化为PGE1，在2系列前列腺素中观察到的计数可忽略不计。在存在BPB（10^(-5)M）的情况下，1-14C-GLA向PGE1的转化几乎完全被消除。上述证据表明，外源性GLA被切除卵巢的大鼠子宫通过一种延长酶代谢，形成二高γ-亚麻酸（DHLA），其反过来又是环氧化酶过氧化物酶反应的底物，最终产生PGE1。未检测到将DHLA转化为花生四烯酸及其进一步衍生物的δ5-去饱和酶活性的证据。巧合的是，外源性GLA能够比从未经处理的去势大鼠分离的子宫条带中所证明的那样，更好地支持随时间变化的收缩稳定性。
