EFFECT OF GAMMA-LINOLENIC ACID, DIHOMOGAMMALINOLENIC ACID, ASCORBYL-6-GAMMA-LINOLENIC ACID AND ASCORBYL-6-DIHOMO GAMMA-LINOLENIC ACID ON HISTAMINE-INDUCED AND METHACHOLINE-INDUCED CONTRACTION OF THE ISOLATED GUINEA-PIG TRACHEAL CHAIN

The relaxant effects of gammalinolenic acid (GLA) and dihomo gammalino lenic acid (DGLA) were compared to the relaxant effect of arachidonic acid (AA). The effect of the combination of ascorbate to form the nove l drugs ascorbyl-6-gammalinolenic acid (ascorbyl-6-GLA) and ascorbyl-6 -dihomo gammalinolenic acid (ascorbyl-6-DGLA) were investigated and th e role of the epithelial cells was determined. Salbutamol was used as control. The isolated tracheas of six to eight guinea pigs were used i n each experiment and suspended in organ baths filled with Krebs-Hense leit solution and aerated with 95% O-2 and 5% CO2. The relaxant effect s produced for histamine-contracted preparations were as follows: AA = 71.2 +/- 0.2%, GLA = 55.2 +/- 4.2%, DGLA = 69.8 +/- 3.9%, ascorbyl-6- GLA = 26.2 +/- 5.1% and ascorbyl-6-DGLA = 54.5 +/- 2.4%. For methachol ine-contracted preparations: AA = 46.6 +/- 3.2%, GLA = 55.0 +/- 9.5%, DGLA = 61.8 +/- 2.7%, ascorbyl-6-GLA = 40.0 +/- 8.0% and ascorbyl-6-DG LA = 88.0 +/- 15.3%. Ascorbyl-6-GLA and ascorbyl-6-DGLA had mainly a d ecreased relaxant effect compared to GLA and DGLA, except ascorbyl-6-D GLA after methacholine-induced contraction, which showed a significant increased relaxant effect. The removal of the epithelium showed decre ased relaxant effects for the drugs except AA, which showed increased values after methacholine contraction. Histamine-contracted preparatio ns showed Varied results. Ascorbyl-B-GLA showed an increased relaxant effect, DGLA was unaffected with no additional effect, and AA, GLA and ascorbyl-6-DGLA showed decreased relaxant effects. In conclusion, it is clear that the contractant and the availability of epithelial cells could ultimately determine the results, though the mechanism remains very complex. The benefit of added ascorbate is still unclear and warr ants more investigation.