Ruth Partridge

Effects of vanadium on glucose metabolism in vitro.

Abstract Although vanadium is found abundantly in the animal and plant kingdoms it has no known biological function. Vanadate compounds have been shown to inhibit cholesterol synthesis, enhance phospolipid oxidation and impair ATP production. In the present study, vanadium is observed to affect glucose metabolism directly in a number of in vitro assay systems, including the stimulation of glucose oxidation and transport in adipocytes, stimulation of glycogen synthesis in liver and diaphragm, and inhibition of hepatic gluconeogenesis and intestinal glucose transport. This survey of findings suggest that vanadium can directly influence glucose metabolism and may play a role in its regulation in vitro .

Multiple sites of interaction between prostaglandins and non-steroidal anti-inflammatory agents.

Several non-steroidal anti-inflammatory agents (NSAIA) are shown to inhibit the net production of prostaglandin (PG)- like activity from arachidonic acid by a cell-free preparation of guinea-pig lung. Moreover, these agents also antagonize PGE-1-induced contractions of the isolated gerbil colon. The anti-spasmogenic effects are reversible and specific. At high concentrations, indomethacin and mefenamic acid interfere with the binding of PGE-1 to a broken cell preparation of rat epididymal adipocytes. Taken together the data indicate that NSAIA interact with prostaglandins at multiple sites and are consistent with the suggestions reported previously that NSAIA may have multiple in vivo actions.

6β-Hydroxylation of triamcinolone acetonide by a hepatic enzyme system: The effect of phenobarbital and 1-benzyl-2-thio-5,6-dihydrouracil

Abstract Evidence has been presented that the postmitochondrial supernate of rat liver homogenate, supplemented with NADPH, hydroxylates the steroid triamcinolone acetonide (TrA), yielding 6β-hydroxy-triamcinolone acetonide as the major metabolite. The administration into rats of inducers of hepatic microsomal monooxygenase system, phenobarbital and 1-benzyl-2-thio-5,6-dihydrouracil, enhanced the 6β-hydroxylation of TrA.

Alteration in the magnitude of induction of tyrosine transaminase by glucocorticoids: II. Effects of phenobarbital, o,p′DDD and diethylaminoethyl diphenylpropyl-acetate (SKF 525A) on metabolism of triamcinolone acetonide

Abstract Treatment of rats with phenobarbital or o,p ′DDD diminishes and treatment with SKF 525A augments the increase in hepatic 2.6.1.5, l -tyrosine-2-oxoglutarate amino-transferase (tyrosine transaminase) by triamcinolone acetonide (TrA). In addition, phenobarbital decreases and SKF 525A increases, in the liver and blood, the concentration of radioactivity derived from ( 3 H-labeled TrA ( 3 H-TrA). The transformation of 3 H-TrA into polar metabolite(s) by 9000 g liver supernate was found to be NADPH and O 2 dependent. This transformation is stimulated by treating the rats with either phenobarbital or o,p ′DDD and inhibited by treatment with SKF 525A. Moreover, the in vitro addition of SKF 525A strongly inhibits this reaction. It is proposed that the effects of phenobarbital, o,p ′DDD and SKF 525A on the magnitude of increase of tyrosine transaminase by TrA is related to the alteration in the rate of metabolism of TrA.

Prostaglandin E antagonist activity of 11, 15-bisdeoxy prostaglandin E1 and congeners.

d,l-11, 15-bisdeoxy PGE1 and certain of its congeners were shown to inhibit gerbil colon contractions induced by l-PGE1. While some of these compounds were selectively antagonistic of PGE1-induced contractions, others additionally inhibited the gerbil colon agonist activities of l-PGE2alpha and acetylcholine. The PGE1 inhibitory activity was apparently competitive in nature. With relatively weak potencies, the bisdeoxy PGE congeners displaced 3H-PGE1 from a fat cell binding site, suggesting competition for a common, putative receptor. Structure-activity relationships and potential utility of these analogs are discussed.

Prostaglandins and congeners XIII (1). The synthesis of dℓ-erythro-16-methoxyprostaglandins

dl-Erythro-16-methoxy-PGE2, PGA2, PGF2alpha, 11-deoxy PGE1, and 11-deoxy PGF1alpha have been prepared via the cuprate conjugate addition procedure. These congeners are less potent than the parent prostaglandins as stimulators of isolated gerbil colon contractions and as bronchodilators in the guinea pig Konzett assay.

Diminished biological activity of C21-steroids in rats pretreated with a thiouracil derivative. Stimulation of steroid hydroxylation?

Abstract Treatment of male rats with 1-benzyl-2-thio-5,6-dihydrouracil (BTDU) diminished the duration of anesthesia produced by administered progesterone. BTDU treatment also decreased the induction of hepatic l -tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5 (tyrosine transaminase), by triamcinolone acetonide (TrA). The diminution of the induction of tyrosine transaminase was attributed to a BTDU-mediated increased transformation of TrA into a less active derivative 6β-hydroxy-triamcinolone acetonide (6β-OH-TrA). In fact, 6β-OH-TrA was found to be markedly less active than TrA in inducing tyrosine transaminase. Furthermore, the administration of 6β-OH-TrA together with TrA did not alter the induction of tyiosine transaminase by TrA, demonstrating that the metabolite does not interfere with the action of TrA. It is suggested that BTDU treatment produces an increase in the activity of the hepatic monooxygenase system which hydroxylates steroids. Thus in BTDU-treated rats progesterone and TrA are converted at faster rates into hydroxylated derivatives which are either intrinsically less active and/or are excreted at a faster rate than the parent compounds.