Acetylsalicylic acid antagonizes the bleeding-induced changes in hemoglobin proportions in normal adult rats.

Normal adult Sprague-Dawley rats were made anemic by repeated phlebotomy. Ion-exchange chromatography of anemic blood showed newborn like hemoglobin proportions, involving the same six hemoglobin components as is found when newborn and adult blood are compared. However, acetylsalicylic acid intake during anemia failed to demonstrate the changes in hemoglobin proportions, either totally or partially, depending upon the doses. Since acetylsalicylic acid inhibits prostaglandin synthesis, the data suggest that one or more prostaglandins may be involved in the process of reverse switching of hemoglobin in adult rat erythroid cells during erythropoietic stress.

Effects of cadmium, zinc, copper and manganese on hepatic parenchymal cell gluconeogenesis.

The effects of divalent cations on gluconeogenesis in enzymatically isolated rat hepatic parenchymal cells were examined. Cadmium, zinc and copper decreased glucose production from lactate (10 mM). However, manganese at 0.05 to 1.0 mM levels stimulated gluconeogenesis by the cells and reduced the effects of the Cd+2, Zn+2 and Cu+2 on gluconeogenesis. The results indicate that under these in vitro conditions the cations altered an aspect of hepatic function--gluconeogenesis from lactate.

Agonist versus antagonist binding to alpha-adrenergic receptors.

The binding properties of two alpha-adrenergic radioligands, [3H]epinephrine (an agonist) and [3H]dihydroergocryptine (an antagonist), were compared in two model systems--membranes derived from human platelets and membranes from rat liver. The platelet contains exclusively alpha 2 and the liver mostly (approximately 80%) alpha 1 receptors. Agonists induce the formation of a guanine nucleotide-sensitive high-affinity state of alpha 2 but not alpha 1 receptors. [3H]Dihydroergocryptine labels all the alpha receptors, whereas [3H]epinephrine at low concentrations labels predominantly the high-affinity form of the alpha 2 receptor in both platelet and liver. However, in the liver, alpha-adrenergic effects such as glycogen phosphorylase activation are shown to be mediated via alpha 1 receptors. Thus, in liver membranes the endogenous "physiological" agonist may not label the physiologically relevant alpha 1 receptors in typical radioligand binding assays using low concentrations of [3H]epinephrine.

Cyclic nucleotides and gluconeogenesis by rat liver cells.

Gluconeogenesis from lactate, pyruvate, fructose, alanine, and other substrates was accelerated by glucagon or epinephrine in hepatocytes isolated from rat liver. Glucagon and epinephrine also increased cyclic AMP accumulation by rat hepatocytes. Isoproterenol increased cyclic AMP but not gluconeogenesis, while phenylephrine accelerated gluconeogenesis. The activation of gluconeogenesis by epinephrine was unaffected by propranolol but blocked by dihydroergotamine. Dibutyryl cyclic AMP added to hepatocytes stimulated gluconeogenesis at concentrations as low as 1 muM. Exogenous cyclic GMP (0.1- muM) inhibited gluconeogenesis due to either glucagon or epinephrine without affecting basal gluconeogenesis. However, carbamylcholine did not affect gluconeogenesis by hepatocytes. Basal gluconeogenesis and the increases due to all agents were inhibited by removal of extracellular calcium or the presence of A-23187, D-600, or tetracaine. In contrast, added 0.1 muM cyclic GMP, 2 mM NH-4-Cl, and 10 muM phenethylbiguanide inhibited glucagon- or epinephrine-stimulated gluconeogenesis without affecting basal values. Studies with hepatocytes indicate that the hormonal activation of gluconeogenesis is not limited to substrates entering prior to triose phosphate formation. Glucagon may act by increasing cyclic AMP which acts via unknown mechanisms to increase gluconeogenesis. In contrast, epinephrine acts via a cyclic AMP-independent mechamism which does not appear to involve cyclic GMP, Ca-2+ flux, of K+ flux.