Effect of gammalinolenic acid, dihomogammalinolenic acid, ascorbyl-6-gammalinolenic acid, and ascorbyl-6-dihomo gammalinolenic acid on histamine- and methacholine-induced contraction of the isolated guinea pig tracheal chain.
The relaxant effects of gammalinolenic acid (GLA) and dihomo gammalinolenic acid (DGLA) were compared to the relaxant effect of arachidonic acid (AA). The effect of the combination of ascorbate to form the novel drugs ascorbyl-6-gammalinolenic acid (ascorbyl-6-GLA) and ascorbyl-6-dihomo gammalinolenic acid (ascorbyl-6-DGLA) were investigated and the role of the epithelial cells was determined. Salbutamol was used as control. The isolated tracheas of six to eight guinea pigs were used in each experiment and suspended in organ baths filled with Krebs-Henseleit solution and aerated with 95% O2 and 5% CO2. The relaxant effects 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 methacholine-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-DGLA=88.0+/-15.3%. Ascorbyl-6-GLA and ascorbyl-6-DGLA had mainly a decreased relaxant effect compared to GLA and DGLA, except ascorbyl-6-DGLA after methacholine-induced contraction, which showed a significant increased relaxant effect. The removal of the epithelium showed decreased relaxant effects for the drugs except AA, which showed increased values after methacholine contraction. Histamine-contracted preparations showed varied results. Ascorbyl-6-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 warrants more investigation.
Kahler
C P
CP
Department of Pharmacology, Medical University of Southern Africa, Medunsa, Republic of South Africa.
Du Plooy
W J
WJ
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D016210:Methacholine Chloride / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D017965:gamma-Linolenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D016085:Bronchoconstrictor Agents; D005231:Fatty Acids, Unsaturated; D016210:Methacholine Chloride; D016718:Arachidonic Acid; D017965:gamma-Linolenic Acid; D006632:Histamine; D015126:8,11,14-Eicosatrienoic Acid; D001205:Ascorbic Acid