Gamma-linolenic acid improves the constancy of contractions in uteri from sprayed rats and is metabolized to prostaglandin E1 but not to bisenoic prostanoids.
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.
Chaud
M
M
Centro de Estudios Farmacológicos, Principios Naturales (CEFAPRIN), Buenos Aires, Argentina.
Franchi
A M
AM
Gimeno
M F
MF
Gimeno
A L
AL
D000527:Alprostadil / Q000096:biosynthesis*; D000818:Animals; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008042:Linolenic Acids / Q000378:metabolism / Q000494:pharmacology*; D010052:Ovariectomy; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000378:metabolism*; D017965:gamma-Linolenic Acid
D004042:Dietary Fats, Unsaturated; D008042:Linolenic Acids; D011453:Prostaglandins; D017965:gamma-Linolenic Acid; D000527:Alprostadil