This work arose out of study of the effect of severe injury on the metabolism of the rat. Its aim was to determine how carbohydrate metabolism differed in injured and normal rats. From the review of Levenson, Einheber & Malm (1961) it is clear that although the effect of injury on metabolism has been studied for a long time there is still much to be learnt. In the past, studies have been, for the most part, confined to determinations of the concentrations of metabolites in tissues. In the case of carbohydrate metabolism this is not enough. Besides concentrations of metabolites the rates of metabolism along the various pathways, glycolytic, gluconeogenic and oxidative, are also required. These rates can only be studied in whole animals by using tracers.We have, therefore, injected control and injured rats intravenously with U-14C-glucose, U-14C-fructose and 1_14C_, 2_14C-and 3-14C-pyruvates. We have followed the disappearance of 14C-glucose and 14C-fructose from the blood and the appearance and subsequent disappearance of 14C-glucose after the injection of 14C-fructose and the labelled pyruvates. The excretion of 14CO2 formed by the oxidation of these compounds in vivo was also followed. In this way the glycolytic and gluconeogenic pathways were spanned by 14C-glucose and 14C-pyruvate while 14C-fructose could be expected to provide information on processes in the middle, as its label enters them mainly as triose phosphate (Hers & Kusaka, 1953;Leuthardt, Testa & Wolf, 1953).Results obtained from experiments of this type show only the combined effects of distribution and metabolism. To separate these two effects one must find a method of interpretation which allows for their interaction. Unless this is done even qualitative conclusions may be wrong and it is quite impossible to make quantitative estimates. The only technique which offers some hope of separating distributive and metabolic processes is compartmental analysis (Sheppard, 1962). Theoretical models which reproduce the most important features of these processes are set up and analysed mathematically. No model can take account of all the processes, 13 Physiol. 179

Interleukin 6 (IL-6) and tumor necrosis factor (TNF) are released from the zona glomerulosa of rat adrenal glands. The release of these cytokines from adrenal cells is regulated by interleukin 1 beta (IL-1 beta) and lipopolysaccharide (LPS), which are involved in the immune and inflammatory responses. Adrenocorticotropic hormone (ACTH) and angiotensin II, hormones that regulate the adrenal cortex, likewise regulate release of cytokines from adrenal glands. Dopamine inhibits aldosterone release from the adrenal cortex. Therefore, effects of dopamine on IL-6 and TNF release from rat adrenal zona glomerulosa were investigated. Primary cultures of rat adrenal zona glomerulosa cells were exposed to test agents and IL-6 and TNF release determined by the 7TD1 and WEHI bioassays, respectively. Dopamine increased basal IL-6 release and potentiated IL-6 release stimulated by ACTH, LPS or IL-1 beta. Dopamine inhibited basal and secretagogue-stimulated (LPS and IL-1 beta) TNF release. These effects of dopamine were mediated by D2 receptors because N-0437, a D2 agonist, had effects on TNF and IL-6 release identical to those of dopamine. Therefore, dopamine, through D2 receptors, regulates the release of IL-6 and TNF from adrenal cells. Because TNF and IL-6 regulate adrenal steroid release, these cytokines may serve as autocrine or paracrine mediators of adrenal gland function.

Interleukin-6 (IL-6) and tumor necrosis factor (TNF) are secreted by rat adrenal zona glomerulosa cells. Serotonin increases the release of aldosterone, corti-costerone, and cortisol from the adrenal cortex. Therefore, the effects of serotonin on IL-6 and TNF release from rat adrenal zona glomerulosa cells were investigated. Cultures of rat adrenal zona glomerulosa cells were enzymatically prepared and cultured for 4-6 d. The cells were then exposed to serum-free RPMl-1640 medium containing vehicle (RPMl medium alone), serotonin, and/or endotoxin, interleukin-1β, or adrenocorticotrophic hormone (ACTH). Following a 5-h incubation, medium was removed from the cells, and IL-6 and TNF content of this medium determined with bioassays. Serotonin (1-1000 nM) increased basal IL-6 release from zona glomerulosa cells, but inhibited basal TNF release from these cells. Endotoxin and interleukin-1β (IL-1β) increased IL-6 and TNF release from zona glomerulosa cells. Serotonin potentiated IL-6 release stimulated by endotoxin and IL-1β, but inhibited TNF release stimulated by these agents. Serotonin potentiated ACTH-stimulated IL-6 release. Serotonin had no effect on IL-6 release from rat anterior pituitary cells. Because IL-6, TNF, and serotonin modify the release of aldosterone and glucocorticoids from adrenal cells, the stimulatory effects of serotonin on aldosterone and glucocorticoid release may be mediated in part by the effects of serotonin on IL-6 and TNF release from adrenal cells.