The effect of glucagon, dibutyrylic cyclic AMP and theophylline on bile production in the cat.

The effect of glucagon, dibutyrylic cyclic AMP and theophylline on bile production and liver metabolism was studied in fasting, chloralose anesthetized cats. After 45 min infusion of glucagon (0.1 mug/kg/min) total bile flow started to increase and finally reached a level 32% above control bile flow. The rise in flow was accompanied by a parallel increase in the biliary clearance of erythritol and the rate of biliary excretion of inorganic ions, whereas the bile acid excretion remained constant. Glucagon therefore appears to stimulate selectively the bile acid-independent canalicular production of bile. In contrast to the delayed action on bile production, glucagon caused an immediate change in liver metabolism as judged from the elimination rate of ethanol and the rise in plasma glucose concentration. Dibutyrylic cyclic AMP or theorphylline also caused similar immediate changes in liver metabolism but neither substance influenced bile production or the biliary excretion of electrolytes or bile acids. It thus appears that glucagon choleresis in the cat is either independent of cAMP release or that an increase in intracellular cAMP is not in itself sufficient to influence bile secretion. The results also seem to exclude that an increase in insulin production induced by hyperglycemia, or hemodynamic changes in the liver, can explain glucagon choleresis.     

On the secretagogue effect of dibutyryl cyclic AMP in the rat exocrine pancreas

Summary DbcAMP0.1 mM induces the discharge of exportable enzymes from rat pancreas fragments incubated in vitro. This effect is qualitatively similar to the action of physiological secretagogues acting via hormone receptors: 1) it is accompanied by the appearance of exocytotic images at the acinar cell apex; 2) it is energy dependent but energy supply is low while that required for the carbamylcholine or caerulein response is high and can only be afforded by oxidative phosphorylation; 3) it is calcium dependent, but no alteration of inward or outward calcium movement can be observed; 4) it is altered by agents known to disrupt the microfilamentous microtubular system [41]. However, the secretory response to DbcAMP is quantitatively less than that obtained with hormonal stimuli. A damaging effect of DbcAMP on pancreatic acinar cells is ruled out on histological and biochemical grounds: there is no significant leakage of LDH; protein synthesis, 2-deoxy-d-glucose andl-leucine uptake are unaltered. The secretagogue effect of DbcAMP is reversible, dose-related and specific. It is not mediated by neuro-transmitter release or by interaction with their receptors. The evidence presented points to a direct interaction of DbcAMP on the pancreatic acinar cell and suggests the last step of the secretory cycle as the most probable site of action of the nucleotide derivative.Abbreviations cAMP Adenosine-3,5-monophosphate - cyclic DbcAMP: N⁶-2-O-Dibutyryl-adenosine-3,5-monophosphate, cyclic - DbcGMP N²-2-O-Dibutyryl-guanosine-3,5-monophosphate, cyclic - 5-AMP Adenosine-5-monophosphate - TCA Trichloracetic acid - ATP Adenosine triphosphate - NADH Nicotinamide-adenine dinucleotide - Tris Tris-(hydroxy-methyl) amino-methane - EGTA Ethylene glycol-bis ( aminoethylether)-NN-tetraacetic acid - LDH Lactic dehydrogenase Part of this work has been presented in abstract from at the VIIIth Symposium of the European Pancreatic Club, Toulouse, France, October, 1975, 23rd–25th and at the Biochemical Society of Belgium [40]This work was partially carried out under contracts from the Ministère de la Politique Scientifique within the framework of the Association Euratom—University of Brussels—University of Pisa, and the Institut National de la Santé et de la Recherche Médicale (France)     

Effect of taurine on the cyclic AMP and GMP levels in the rat heart during stress

Taurine had no effect on the cyclic nucleotide level in the heart of intact rats but sharply reduced the increase in cyclic AMP and cyclic GMP levels taking place during stress. The action of taurine on the cyclic GMP content in the heart was not exhibited after preliminary atropinization of the animals; its effect on cyclic AMP was greatly reduced after partial blockade of -adrenoreceptors. It is suggested that taurine is a nonspecific regulator of the sensitivity of the myocardial cells to biologically active substances.All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR. (Presented by Academician of the Academy of Medical Sciences of the USSR, E. I. Chazov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 2, pp. 134–137, February, 1979.     

Circahoralian rhythm of cyclic AMP concentration in rat parotid gland slices

The cyclic AMP concentration was measured by a radioimmunoassay method in slices of rat parotid gland after incubation for 12–14 h. In each concrete experiment only one gland was used. Pieces for measurement of cyclic AMP concentration were taken at 10-min intervals for 2 h. Rhythmic changes in the cyclic AMP concentration with a period of 20–50 min were found. The period of the cyclic AMP rhythm is similar to the period of fluctuations in other parameters discovered previously on the same object: the dry weight of the cells, rate of protein synthesis, and ornithine decarboxylase activity.Laboratory of Cytology, N. K. Kol'tsov Institute of Developmental Biology, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 12, pp. 711–712, December, 1979.     

Modification of liver cell volume by insulin and glucagon

Summary Cell volume plays a decisive role in the regulation of hepatic metabolism. The present study has been performed to test for an effect of insulin and glucagon on liver cell volume. To this end, the effect of these hormones has been studied in isolated perfused rat livers and isolated rat hepatocytes. Insulin leads to rapid stimulation of cellular K+ uptake and increase of cell volume, effects reversed by glucagon or cAMP. The insulin stimulated cellular K+ uptake is significantly decreased in the presence of either loop diuretics (furosemide or bumetanide) or amiloride and is completely inhibited in the presence of both, bumetanide and amiloride. The glucagon stimulated cellular K+ release in the presence of insulin is blunted by K+ channel blocker quinidine. The effects of insulin and glucagon on liver cell volume could participate in the regulation of hepatic metabolism by these hormones.     

Cyclic AMP metabolism in the liver of newborn rats after irradiation during organogenesis

The level of adenylate cyclase (AC) and phosphodiesterase (PDE) activity and the reserves of cyclic AMP in the liver of newborn rats were investigated in normal animals and after irradiation on the 9th day of embryonic development. After irradiation in a dose of 50 R the basal AC and PDE activity was reduced, but there was no change in the steady-state cyclic AMP content in the tissues. The adrenalin-stimulated AC activity showed only a tendency to fall after irradiation. It is suggested that at critical moments of development, when the hormonal inducer is present in the liver of irradiated animals the conditions may be created for an increase in the cyclic AMP reserves.Laboratory of Molecular Radiobiology, Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 7, pp. 91–93, July, 1978.     

Inhibition of cyclic AMP phosphodiesterase of the rat heart and brain by neurohormone C in vitro

The effect of neurohormone C, a new coronary dilator isolated from bovine hypothalamus, on activity of the phosphodiesterase (PDE) of cyclic adenosine-3,5-monophosphate (AMP) was investigated. Considerable inhibition of PDE was shown in the supernatant of rat brain and heart homogenates (2000g) under the influence of neurohormone C. The existence of correlation between the coronary dilator effect of the hormone and regulation of the cyclic AMP level under the influence of a change in PDE activity is postulated.Laboratory of Hormones, Institute of Biochemistry, Academy of Sciences of the Armenian SSR, Erevan. (Presented by Academician of the Academy of Medical Sciences of the USSR S. E. Severin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 6, pp. 691–693, June, 1977.     

Demonstration of abnormal cyclic AMP production in platelets from patients with fragile X syndrome

Cyclic AMP production was studied in platelets from 31 patients with fragile X syndrome, 16 patients with mental retardation, 4 patients with autistic disorder, and 57 control individuals. 1-isobutyl-3-methylxanthine (IBMX) was used to inhibit phosphodiesterase; prostaglandin E₁ (PGE₁), to stimulate cAMP production via a receptor-dependent mechanism, and forskolin (FSK), to directly activate the catalytic subunit. Cyclic AMP production in IBMX, PGE₁ + IBMX, and FSK + IBMX was 50% (P<0.05), 65% (P=0.001), and 53% (P = 0.001), respectively, in fragile X platelets relative to controls. Cyclic AMP production was not statistically different from controls in patients with mental retardation or autistic disorder. There was no effect of age or sex on cAMP production. Dose response curves suggested that abnormal cAMP production was due to diminished maximal response rather than altered potency of stimulating agents. The data presented here demonstrate that diminished cAMP production exists in platelets from patients with fragile X syndrome. Thus, defective functioning of cAMP-mediated regulatory signalling pathways in fragile X brain may contribute to the mental deficiency in these patients. © 1993 Wiley-Liss, Inc.     

Functional activity of isolated perfused rat liver depends on medium composition

It is convenient to study liver function and metabolism on the model of isolated perfused organ. The results of the present study indicate that viability and metabolic activity of the organ largely depend on the composition of the medium. Under conditions of isolated perfusion, the known pathway of oxygen transport through capillary filtration is supplemented by oxygen delivery to cells through the organ surface making an important contribution to liver oxygenation. Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 146, No. 7, pp. 117–120, July, 2008     

Contribution of liver nerves,glucagon, and adrenaline to the glycaemic response to exercise in rats

The contribution of hepatic sympathetic innervation, glucagon and adrenaline to the glycaemic response to exercise was investigated in rats. Hepatically denervated (LDX) or sham operated (SHAM) rats with permanent catheters were therefore submitted to swimming with or without infusion of somatostatin in combination with adrenodemedul–lation. Blood samples were taken for measurements of blood glucose, plasma free fatty acids (FFA), adrenaline (A), noradrenaline (NA), insulin and glucagon. Liver denervation by itself did not influence glucose levels during exercise. Infusion of somatostatin in SHAM animals, which inhibited the exercise–induced glucagon response, led to enhanced sympathoadrenal outflow (measured as plasma A and NA) and a reduced blood glucose during exercise, suggesting that glucagon serves as a powerful mediator of the glycaemic response during swimming. Infusion of somatostatin in LDX animals failed to enhance plasma NA levels and led to a more pronounced reduction in blood glucose levels. This indicates that liver nerves do contribute to the glycaemic response to exercise when glucagon secretion is suppressed. Reduced blood glucose levels after adrenodemedullation revealed that adrenal A is another important mediator of the glucose response to exercise. Infusion of somatostatin in adreno–demedullated SHAM or LDX animals was not accompanied with increased NA outflow, suggesting that adrenal A is necessary to allow the compensatory increased outflow of NA from sympathetic nerves. In conclusion, the study shows that pancreatic glucagon and adrenal A are the predominant factors influencing the glycaemic response to exercise, whereas a role of the sympathetic liver nerves becomes evident when glucagon secretion is suppressed.