Gamma-linolenic acid improves the constancy of contractions in uteri from spayed rats and is metabolized to prostaglandins E 1 but not to bisenoic prostanoids

Abstract

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 unsatured 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 −7M), 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 5M) 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 chalennge with 10 −7M GLA (delivered immediately after isolation) enhanced significantly the output of PGE 1 but did not influence the generation and release of PGE 2 or PGF 2α. BPB (10 −5M) had no significant effect on the basal output of PGE 1, PGE 2 or PGF 2 but completely prevented the enhancing action of GLA on the synthesis and release of PGE 1. Labelled GLA was mainly converted to PGE 1 by rat uterine segments and negligible counts in the 2-series of prostanoids, were observed. In presence of BPB (10 −5M) the conversion of 1- 14C-GLA, to PGE 1 was almost completely abolished. The foregoing evidence 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, PGE 1. No evidence of a Δ5-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.