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S Corvera

Publications and source records attributed to S Corvera.

54 records · Page 3Linked to original sources
PubMed1986

Phorbol esters inhibit alpha 1-adrenergic effects and decrease the affinity of liver cell alpha 1-adrenergic receptors for (-)-epinephrine.

4 beta-Phorbol 12-myristate 13-acetate (PMA) modified the metabolic actions of three calcium-dependent hormones in different ways. The stimulations of glycogenolysis ureogenesis and phosphatidylinositol labeling produced by alpha 1-adrenergic agonist was blocked by the phorbol ester. In contrast, PMA slightly increased the stimulation of ureogenesis produced by low concentration of angiotensin II without modifying the maximal response. No effect of PMA was observed on the stimulation of ureogenesis induced by vasopressin. The stimulation of phosphatidylinositol labeling induced by vasopressin was decreased by PMA, whereas that induced by angiotensin II was not affected. In intact freshly isolated hepatocytes, [3H]prazosin binds with high affinity to a site which displays the characteristics of alpha 1-adrenergic receptor. Competitive inhibition studies with (-)-epinephrine reveal two different sites for this agonist: a high affinity site (Kd 9 nM) and a low affinity site (Kd 2 microM). In the presence of phorbol esters, (-)-epinephrine binding data now show the presence of a single class of low affinity sites, with similar affinity to those present in control cells. Thus, the inhibition of hepatocyte alpha 1-adrenergic action by PMA may be related to the loss of high affinity binding sites caused by the tumor promoter.

Angiotensin II↗
PubMed1985

Differential effects of adrenergic agonists and phorbol esters on the alpha 1-adrenoceptors of hepatocytes and aorta.

Epinephrine, norepinephrine and phenylephrine stimulate phosphatidylinositol labeling with [32P]Pi in both rat hepatocytes and rabbit aorta. Methoxamine was a full agonist for this effect in rabbit aorta whereas cirazoline and oxymetazoline were partial agonists. In contrast, these three agents (methoxamine, cirazoline and oxymetazoline) were unable to stimulate phosphatidylinositol labeling in rat hepatocytes. Furthermore, cirazoline and oxymetazoline were able to displace the dose-response curve to epinephrine in rat hepatocytes, i.e., they behaved as antagonists. Binding competition curves of these agents with labeled adrenergic ligands indicate that the affinity of alpha 1-adrenergic receptors in these two tissues (aorta and liver) for the different agents tested was very similar. In addition it was observed that phorbol myristate-acetate inhibited in a dose-dependent fashion the epinephrine-mediated stimulation of phosphatidylinositol labeling in hepatocytes but was without effect on the action of the amine in aorta. Our data suggest that stereochemical differences for alpha 1-adrenergic activation in liver and aorta may exist and indicate that the ability of phorbol esters to inhibit alpha 1-adrenergic effects is not universal.

Adrenergic alpha-Agonists↗
PubMed1985

Mechanism of insulin action on membrane protein recycling: a selective decrease in the phosphorylation state of insulin-like growth factor II receptors in the cell surface membrane.

Insulin action in adipocytes leads to an increase in the steady-state number of cell surface glucose transporters and insulin-like growth factor II (IGF-II) receptors that appear to cycle continuously between the plasma membrane and a low-density membrane fraction. The IGF-II receptor could be labeled to constant specific activity by incubating adipocytes with [32P]phosphate for 2 hr. The extent of phosphorylation of IGF-II receptors in plasma membranes and in low-density microsomes was compared using 125I-labeled IGF-II binding and immunoblotting to quantitate the receptors present in each fraction. Receptors in the plasma membrane fraction of control cells incorporated approximately 1 molecule of phosphate per IGF-II binding site or 2 to 3 times more phosphate than was incorporated into IGF-II receptors in the low-density microsomes. Addition of insulin to labeled adipocytes did not change the specific activity of the gamma-phosphate of ATP but produced a specific and sharp decrease in the 32P-phosphate content of IGF-II receptors in the plasma membrane. No change due to insulin in the phosphorylation of receptors derived from low-density microsomes was observed. The insulin-mediated decrease in the [32P]phosphate content of IGF-II receptors from the plasma membrane was rapid in onset, paralleled the increase in the number of IGF-II receptors on the cell surface, and persisted for at least 30 min in the presence of insulin. Furthermore, when the effect of insulin to increase the number of IGF-II receptors in the cell surface was prevented by cooling cells to 5 degrees C, the decrease in phosphorylation of plasma membrane receptors could still be observed, indicating that this latter effect is not secondary to receptor redistribution. These data indicate that insulin inhibits one or more IGF-II receptor kinases or increases phosphatase activity, or both. Decreased phosphorylation of such insulin-sensitive plasma membrane components as IGF-II receptors may play a role in increasing their steady-state cell surface concentration, perhaps by delaying their internalization.

Adenosine Triphosphate↗
PubMed1984

Possible involvement of cyclooxygenase products in the actions of platelet-activating factor and of lipoxygenase products in the vascular effects of epinephrine in perfused rat liver.

Platelet-activating factor (PAF) stimulates glycogenolysis and induces vasoconstriction in perfused rat liver. The effect of PAF was rapid but transient and it was blocked by indomethacin and bromophenacyl bromide which suggests a role of cyclooxygenase metabolites in its action. The homologous desensitization of glycogenolysis produced by PAF and the sensitivity of its actions to inhibitors of cyclooxygenase and phospholipase A2 markedly differentiate the mechanism of action of this agent with that of alpha 1-adrenergic agents, vasopressin or angiotensin II. No effect of PAF in isolated hepatocytes was observed which suggest that cells other than hepatocytes could be involved in its action in perfused liver. In addition nordihydroguaiaretic acid and bromophenacyl bromide abolished the vascular effect (but not the glycogenolysis) produced by epinephrine which suggest a role for lipoxygenase products in this effect.

Acetophenones↗
PubMed1984

Metabolic effects and cyclic AMP levels produced by glucagon, (1-N alpha-Trinitrophenylhistidine,12-homoarginine)glucagon and forskolin in isolated rat hepatocytes.

[1-N alpha-Trinitrophenylhistidine,12-homoarginine]glucagon (THG) is a potent antagonist of the effects of glucagon on liver membrane adenylate cyclase. In isolated hepatocytes, this glucagon analogue was an extremely weak partial agonist for cAMP accumulation, and it blocked the stimulation of cAMP accumulation produced by glucagon. However, THG was a full agonist for the stimulation of glycogenolysis, gluconeogenesis and urea synthesis in rat hepatocytes, and did not antagonize the metabolic effects of glucagon under most of the conditions examined. Forskolin potentiated the stimulation of cAMP accumulation produced by glucagon or THG, but did not potentiate their metabolic actions. A much larger increase in cAMP levels seemed to be required for the stimulation of hepatocyte metabolism by forskolin than by glucagon or THG. This may suggest the existence of a functional compartmentation of cAMP in rat hepatocytes. The possible existence of compartments in cAMP-mediated hormone actions and the involvement of factors, besides cAMP, in mediating the effects of THG and glucagon is suggested.

Animals↗
PubMed1984

Phorbol esters inhibit alpha 1 adrenergic stimulation of glycogenolysis in isolated rat hepatocytes.

Tumor promoting phorbol esters can stimulate Ca++-phospholipid-dependent protein kinase. It has been suggested that this enzyme may mediate the effects of calcium-dependent hormones. In this paper the effects of phorbol 12-myristate 13-acetate (TPA) on isolated rat hepatocyte metabolism were studied. Phorbol esters completely blocked alpha 1-adrenergic stimulation of glycogenolysis. This effect is quite specific for alpha 1-adrenergic actions, as the stimulations of glycogenolysis by vasopressin, angiotensin II, ionophore A-23187 and glucagon were unaffected by TPA. The potencies of the different phorbol esters used in this study suggests that the inhibitory effects of these agents may be due to activation of protein kinase C. The effect of phorbol esters on alpha 1-adrenergic actions seems to occur at an early step of the alpha 1-adrenergic action. TPA (10(-11) -10(-6)M) was unable to stimulate glycogenolysis. Urea synthesis, which is stimulated by vasopressin and alpha 1-adrenergic agents, was not stimulated by phorbol ester, neither alone nor in combination with the Ca++ ionophore A-23187.

Angiotensin II↗
PubMed1984

Modulation by thyroid status of cyclic AMP-dependent and Ca2+-dependent mechanisms of hormone action in rat liver cells. Possible involvement of two different transduction mechanisms in alpha 1-adrenergic action.

The actions of hormones which are associated to cAMP-dependent and calcium-dependent mechanisms of signal transduction were studied in hepatocytes obtained from rats with different thyroid states. In cells from euthyroid and hyperthyroid rats, the metabolic actions of epinephrine were mediated mainly through alpha 1-adrenoceptors; beta-adrenoceptors seem to be functionally unimportant. In contrast, both alpha 1- and beta-adrenoceptors mediate the actions of epinephrine in hepatocytes from hypothyroid animals. Phosphatidylinositol labeling was strongly stimulated by epinephrine, vasopressin and angiotensin II in cells from eu-, hyper- or hypothyroid rats. However, metabolic responsiveness to vasopressin and angiotensin II was markedly impaired in the hypothyroid state. The glycogenolytic response to the calcium ionophore A-23187 was also impaired, suggesting that hepatocytes from hypothyroid rats are less sensitive to calcium signalling. The persistence of alpha 1-adrenergic responsiveness in the hypothyroid state suggests that the mechanism of signal transduction for alpha 1-adrenergic amines is not identical to that of the vasopressor peptides. alpha 1-Adrenergic stimulation of cyclic AMP accumulation was not detected in cells from hypothyroid rats. These data suggest that factors besides calcium and besides cAMP are probably involved in alpha 1-adrenergic actions. Metabolic responses to glucagon and to the cAMP analogue dibutyryl cAMP were not markedly changed during hypothyroidism, although cAMP accumulation produced by glucagon and beta-adrenergic agonists was enhanced. In hyperthyroidism, cell responsiveness to epinephrine, vasopressin, angiotensin II and glucagon was decreased, but sensitivity to cAMP was not markedly altered. The factors involved in this hyposensitivity to hormones during hyperthyroidism are unclear.

Angiotensin II↗
PubMed1984

Effect of insulin on alpha1-adrenergic actions in hepatocytes from euthyroid and hypothyroid rats. Possible involvement of two pathways in alpha1-adrenergic actions.

The effect of insulin on the alpha1-adrenergic stimulation of glycogenolysis and ureogenesis, which is very small or undetectable in hepatocytes from control animals, is marked in hepatocytes from hypothyroid rats; the metabolic actions due to alpha1-adrenergic activation, but not those due to glucagon, were nearly blocked by insulin in cells from hypothyroid rats. The alpha1-adrenergic-mediated stimulation of phosphatidylinositol labelling was not affected by insulin in cells from either control or hypothyroid rats. The data suggest that the alpha1-adrenergic action proceeds through two pathways, one of which is very sensitive to insulin and predominates in cells from hypothyroid rats.

Animals↗
PubMed1983

Sensitivity of liver cells formed after partial hepatectomy to glucagon, vasopressin and angiotensin II.

During the active proliferation which follows partial hepatectomy, the sensitivity of liver cells to glucagon is markedly diminished. In hepatocytes obtained from rats partially hepatectomized 3 days before experiments were performed, the dose-response curves to glucagon were shifted to the right by about two orders of magnitude as compared to those of the control cells. Later on (7 days after surgery) the dose-response to glucagon was still shifted to the right but by only one order of magnitude. These data are consistent with the diminution in the number of glucagon receptors in liver plasma membrane during liver regeneration reported by other authors. No stimulation of glycogenolysis, gluconeogenesis or ureogenesis was produced by vasopressin or angiotensin II in hepatocytes from rats partially hepatectomized 3 days before experimentation. However, phosphatidylinositol labeling was stimulated in these cells to a similar extent as in the controls. The ionophore A23187 was also ineffective in stimulating glycogenolysis in these cells. Later, 7 days after surgery, the hepatic responsiveness to vasopressin and angiotensin II was restored. The data suggest that, during the initial stages of liver regeneration, the enzymatic machinery of the hepatocyte is not sensitive to calcium-signalling.

Angiotensin II↗
PubMed1983

Effect of pertussis toxin on hormonal responsiveness of rat hepatocytes.

The ureogenic action of epinephrine in hepatocytes from normal adult rats is mediated through activation of alpha 1-adrenoceptors. beta-Adrenoceptors in addition to alpha 1-adrenoceptors, became involved in mediating this effect in cells from animals treated with pertussis toxin. The accumulation of cyclic-AMP in response to epinephrine or isoproterenol was markedly increased in hepatocytes from pertussis-treated rats as compared to that observed in control cells. The accumulation of cyclic-AMP due to glucagon was also increased. It is suggested that pertussis toxin may release a constraint on adenylate cyclase activity by blocking the inhibitory coupling mechanism (Ni) or some other entity involved in the regulation of the activity of this enzyme.

Adenylate Cyclase Toxin↗
PubMed1982

Vasopressin and angiotensin II stimulate ureogenesis through increased mitochondrial citrulline production.

Vasopressin, angiotensin II, glucagon and epinephrine (through a cAMP-independent, alpha1adrenergic mechanism), stimulate ureogenesis in isolated rat hepatocytes. Mitochondria, isolated from hepatocytes which were previously treated with these hormones, displayed an enhanced rate of citrulline synthesis in the presence of NH4Cl as the nitrogen source. When mitochondria were incubated with glutamine as the nitrogen source, only those mitochondria isolated from hepatocytes previously treated with epinephrine or glucagon displayed an enhanced capacity to synthesize citrulline. When cells were incubated in the absence of extracellular calcium, the effects of vasopressin and angiotensin II on urea synthesis were abolished, whereas those of epinephrine and glucagon were only diminished. Mitochondria isolated from cells incubated under these conditions, showed that the effect of all these hormones on citrulline synthesis could still be observed. However, the effects of glucagon and epinephrine plus propranolol were larger than those of angiotensin II or vasopressin. Phosphatidylinositol labeling was significantly increased by epinephrine, vasopressin and angiotensin II both in the absence or presence of calcium. Cyclic AMP levels were significantly increased by glucagon or epinephrine but not by vasopressin or angiotensin II. The effect of epinephrine on cyclic AMP levels was blocked by propranolol both in the absence or presence of calcium.

Angiotensin II↗
PubMed1981

Alpha 1-adrenoceptor activation stimulates ureogenesis in rat hepatocytes.

Epinephrine produced a dose-dependent stimulation of ureogenesis. Epinephrine action was unaffected by the beta-adrenergic antagonist propranolol but was blocked by the alpha-adrenergic antagonists prazosin and yohimbine. Prazosin was approximately 3 orders of magnitude more potent than yohimbine, indicating that the adrenoceptor involved in this action is of the alpha 1-subtype.

Animals↗