The Ca2+-mobilizing actions of vasopressin and angiotensin differ from those of the α-adrenergic agonist phenylephrine in the perfused rat liver

A Ca2+-sensitive electrode was used to study net Ca2+-flux changes induced by the administration of phenylephrine, vasopressin and angiotensin to the perfused rat liver. The studies reveal that, although the Ca2+ responses induced by vasopressin and angiotensin are similar, they are quite different from the Ca2+ fluxes induced by phenylephrine. The administration of phenylephrine is accompanied by a stimulation of a net amount of Ca2+ efflux (140 nmol/g of liver). A re-uptake of a similar amount of Ca2+ occurs only after the hormone is removed. In contrast, the administration of vasopressin or angiotensin to livers perfused with 1.3 mM-Ca2+ induces the release of a relatively small amount of Ca2+ (approx. 40 nmol/g of liver) during the first 60 s. This is followed by a much larger amount of Ca2+ uptake (70-140 nmol/g of liver) after 1-2.5 min of hormone administration, and a slow efflux or loss of a similar amount of Ca2+ over a period of 6-8 min. At lower concentrations of perfusate Ca2+ (less than 600 microM) these hormones induce only a net efflux of the ion. These results suggest that at physiological concentrations of extracellular Ca2+ the mechanism by which alpha-adrenergic agonists mobilize cellular Ca2+ is different from that involving vasopressin and angiotensin. It seems that the hormones may have quite diverse effects on Ca2+ transport across the plasma membrane and perhaps organellar membranes in liver.

Download Full-text

The action of α-adrenergic agonists on plasma-membrane calcium fluxes in perfused rat liver

Biochemical Journal ◽

10.1042/bj2200043 ◽

1984 ◽

Vol 220 (1) ◽

pp. 43-50 ◽

Cited By ~ 35

Author(s):

P H Reinhart ◽

W M Taylor ◽

F L Bygrave

Keyword(s):

Plasma Membrane ◽

Rat Liver ◽

Potential Role ◽

Dependent Manner ◽

Perfused Rat Liver ◽

Adrenergic Agonists ◽

Mediated Effects ◽

Alpha Agonist ◽

Alpha Adrenergic Agonist

The effect of alpha-adrenergic agonists on Ca2+ fluxes was examined in the perfused rat liver by using a combination of Ca2+-electrode and 45Ca2+-uptake techniques. We showed that net Ca2+ fluxes can be described by the activities of separate Ca2+-uptake and Ca2+-efflux components, and that alpha-adrenergic agonists modulate the activity of both components in a time-dependent manner. Under resting conditions, Ca2+-uptake and -efflux activities are balanced, resulting in Ca2+ cycling across the plasma membrane. The alpha-adrenergic agonists vasopressin and angiotensin, but not glucagon, stimulate the rate of both Ca2+ efflux and Ca2+ uptake. During the first 2-3 min of alpha-agonist administration the effect on the efflux component is the greater, the net effect being efflux of Ca2+ from the cell. After 3-4 min of phenylephrine treatment, net Ca2+ movements are essentially complete, however, the rate of Ca2+ cycling is significantly increased. After removal of the alpha-agonist a large stimulation of the rate of Ca2+ uptake leads to the net accumulation of Ca2+ by the cell. The potential role of these Ca2+ flux changes in the expression of alpha-adrenergic-agonist-mediated effects is discussed.

Download Full-text

The stimulation of tricarboxylic acid-cycle flux by α-adrenergic agonists in perfused rat liver

Biochemical Journal ◽

10.1042/bj2330321 ◽

1986 ◽

Vol 233 (2) ◽

pp. 321-324 ◽

Cited By ~ 17

Author(s):

W M Taylor ◽

E van de Pol ◽

F L Bygrave

Keyword(s):

Rat Liver ◽

Tricarboxylic Acid Cycle ◽

Tricarboxylic Acid ◽

Perfused Rat Liver ◽

Adrenergic Agonists ◽

Acid Cycle ◽

Total Tissue ◽

Stimulation Of

Output of 14CO2 from 1-14C-labelled glutamate, 2-oxoglutarate or octanoate and from 4-methyl-2-oxo[2-14C]pentanoate was increased by more than 100% after infusion of phenylephrine into perfused livers of fed rats. Infusion of ethanol or sorbitol raised 3-hydroxybutyrate/acetoacetate ratios and decreased the output of 14CO2. Increases in 14CO2 output induced by phenylephrine were observed in the presence or absence of ethanol or sorbitol and were accompanied by elevated 3-hydroxybutyrate/acetoacetate ratios under all conditions examined. Phenylephrine had no effect on total tissue ATP/ADP ratios in livers from fed or starved rats. The data suggest that phenylephrine-induced increases in tricarboxylic acid-cycle flux do not arise from lowered matrix NADH/NAD+ or ATP/ADP ratios.

Download Full-text

The synergistic action (cross-talk) of glucagon and vasopressin induces early bile flow and plasma-membrane calcium fluxes in the perfused rat liver

Biochemical Journal ◽

10.1042/bj3010187 ◽

1994 ◽

Vol 301 (1) ◽

pp. 187-192 ◽

Cited By ~ 7

Author(s):

A Karjalainen ◽

F L Bygrave

Keyword(s):

Plasma Membrane ◽

Oxygen Uptake ◽

Rat Liver ◽

Bile Flow ◽

Concomitant Administration ◽

Synergistic Action ◽

Perfused Rat Liver ◽

Maximal Rate ◽

Adrenergic Agonist ◽

Lower Magnitude

A study was made of the initial responses of perfusate Ca2+ fluxes and bile flow to Ca(2+)-mobilizing agonists, following refinements to the methods for analysing these parameters in the perfused rat liver. Net Ca2+ efflux induced by vasopressin commences at 15 s, reaches a maximal rate at 35 s and declines to zero by 55 s, when Ca2+ influx commences. Vasopressin-induced increases in bile flow commence by 20 s, attain a maximal rate by 35 s and begin to decline at 50 s, to reach basal values by 90 s. Concomitant administration of glucagon modifies each of these actions of vasopressin in the following ways: it decreases by 5 s the time of onset of net Ca2+ efflux, and the time and magnitude of such efflux, and the time of onset of bile flow is decreased to 15 s, and the flow reaches maximal rates by 30 s. When the alpha 1-adrenergic agonist phenylephrine is used in place of vasopressin, Ca2+ efflux commences at 17-18 s and is greater in magnitude; little bile flow is induced by this agonist. Glucagon modifies the action of phenylephrine in the following ways: the onset of Ca2+ efflux is brought forward by 2-3 s, it is of lower magnitude and Ca2+ influx begins by 45 s; bile flow commences by 15-20 s, and reaches a maximum at 30 s, where the rate is much greater than in the absence of glucagon; this rate gradually declines to be near basal by 80 s. The onset of agonist-induced oxygen uptake was also brought forward by the co-administration of glucagon. Comparison of agonist-induced plasma-membrane Ca2+ fluxes and bile flow (with or without glucagon administration) suggests that correlations can be made between net Ca2+ fluxes and the transient increases seen in bile flow.

Download Full-text

On the stimulation of respiration by alpha-adrenergic agonists in perfused rat liver

European Journal of Biochemistry ◽

10.1111/j.1432-1033.1986.tb09493.x ◽

1986 ◽

Vol 155 (2) ◽

pp. 319-322 ◽

Cited By ~ 13

Author(s):

Wayne M. TAYLOR ◽

Erika POL ◽

Fyfe L. BYGRAVE

Keyword(s):

Rat Liver ◽

Perfused Rat Liver ◽

Adrenergic Agonists ◽

Stimulation Of

Download Full-text

The contribution of both extracellular and intracellular calcium to the action of α-adrenergic agonists in perfused rat liver

Biochemical Journal ◽

10.1042/bj2200035 ◽

1984 ◽

Vol 220 (1) ◽

pp. 35-42 ◽

Cited By ~ 32

Author(s):

P H Reinhart ◽

W M Taylor ◽

F L Bygrave

Keyword(s):

Rat Liver ◽

Perfused Rat Liver ◽

Adrenergic Agonists ◽

Adrenergic Agonist ◽

Redox Ratio ◽

Lactate And Pyruvate ◽

Body Production ◽

Sustained Responses ◽

Alpha Adrenergic Agonist

The role of both intracellular and extracellular Ca2+ pools in the expression of alpha-adrenergic-agonist-mediated responses was examined in perfused rat liver. Responses studied included glycogenolysis, respiration, lactate and pyruvate formation, ketone-body production, changes in the cytoplasmic and mitochondrial redox ratio and cellular K+ fluxes. Each of these was shown to be dependent on the mobilization of intracellular Ca2+ and can be grouped into one of two response types. Transient responses (ion fluxes and the redox ratios) are obligatorily dependent on the mobilization of intracellular Ca2+ and occur irrespective of the extracellular Ca2+ concentration. Sustained responses, on the other hand, initially require intracellular Ca2+ and, subsequently, extracellular Ca2+. The data indicate that alpha-adrenergic agonists mobilize extracellular Ca2+ as well as intracellular Ca2+ and that both pools are required for the full expression of hormone-induced responses in rat liver.

Download Full-text