Author

Irshad Ali

Date of Award

1995

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Abstract

Hypertrehalosemic hormones produced by the corpus cardiacum increase the concentration of several fatty acids in cockroach fat body trophocytes. The phospholipase A{dollar}\sb2{dollar} (PLA{dollar}\sb2){dollar} activator melittin has a similar effect. The fatty acids include palmitic, stearic, oleic and linoleic acid. The hormone mediated release of these fatty acids is blocked by the PLA{dollar}\sb2{dollar} inhibitors mepacrine and {dollar}\rho{dollar}-bromophenacyl bromide. These observations suggest that hormonal release of fatty acids, may be due to the activation of PLA{dollar}\sb2.{dollar};The increase in non-esterified fatty acids appears to be linked to the increase in trehalose efflux since sugar efflux is stimulated by stearic, oleic, linoleic and arachidonic acid. The increase in intracellular free fatty acids is also correlated with the activation of phosphorylase, the rate limiting step in trehalose synthesis.;This study is the first to show that conversion of linoleic acid to arachidonic acid is stimulated by the hypertrehalosemic hormones. The data suggest that the effect of arachidonic acid and its metabolites are dependent on an increase in production of linoleic, and possibly other fatty acids, which are converted into arachidonic acid.;The cyclooxygenase inhibitors indomethacin and diclofenac are effective inhibitors of hormone activated trehalose efflux. This indicates the importance of the arachidonic acid metabolite pathway in the activation of trehalose efflux. Stimulation of trehalose efflux by prostaglandin-like metabolites from trophocyte homogenate challenged with hormone and also by prostaglandin F{dollar}\sb{lcub}2\alpha{rcub}{dollar} and A{dollar}\sb2{dollar} also suggests that arachidonic acid metabolites are involved in hormonal stimulation of trehalose efflux from the trophocytes. This is one of the first studies to demonstrate a link between a specific physiological function, hormonal activation of trehalose efflux, and the prostglandins.;Trehalose efflux is inhibited by the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA). Unlike the cyclooxygenase inhibitors, NDGA appears to have a potent inhibitory effect on PLA{dollar}\sb2{dollar} since it also inhibits production of fatty acids. Inhibition of trehalose efflux by NDGA may be due to the inhibition of fatty acid production rather than inhibition of lipoxygenase.;A novel discovery in this study was the potent inhibitory effect of fatty acids, particularly linoleic and arachidonic acid, on the trehalose-6-phosphatase reaction. The concentration of fatty acid required to produce 50 percent inhibition is within the range expected to occur in vivo. The results suggest that trehalose-6-phosphatase may be a key step in the regulation of trehalose efflux from the trophocyte to the hemolymph.

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