Independent Variation of Glucagon and Epinephrine Responsive Components of Hepatic Adenyl Cyclase as a Function of Age, Sex and Steroid Hormones

Bitensky, Mark W.; Russell, V.; Blanco, Manuel Vázquez

doi:10.1210/endo-86-1-154

Cited by 121 publications

(28 citation statements)

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“…In adrenalectomized (Adx) rats, the stimulation of gluconeogenesis and glycogenolysis in response to catecholamines is markedly reduced (16). However, the production of cAMP in response to catecholamines is increased in Adx animals (16,18,19).Since changes in the catecholamine-sensitive adenylate cyclase occur in the absence of glucocorticoids, it was of interest to determine the number and properties of fl-adrenergic receptors in liver from normal and Adx animals.[125I]Iodohydroxybenzylpindolol (IHYP), a potent fl-receptor antagonist, has been used as the ligand in a binding assay for fl-adrenergic receptors of rat liver. The increase in hormonestimulated adenylate cyclase after adrenalectomy has been correlated with an increase in the number of ,B-adrenergic receptors.…”

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confidence: 99%

beta-adrenergic receptors in rat liver: effects of adrenalectomy.

Wolfe¹,

Harden²,

Molinoff³

1976

Proc. Natl. Acad. Sci. U.S.A.

135

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The response of rat liver adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] to catecholamines is enhanced after adrenalectomy. To ). An increase in the sensitivity of adrenergically innervated organs to catecholamines has also been observed after denervation (4-7). This increase has been associated with both pre-and postsynaptic changes.f3-Adrenergic receptor-mediated responses to catecholamines involve the activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] which catalyzes the formation of adenosine 3':5'-cyclic monophosphate (cAMP) (8). An increase in hormone-sensitive adenylate cyclase activity and a concomitant increase in the concentration of cAMP after exposure to appropriate hormones have been seen in surgically denervated dog heart (5) and rat pineal organ (9). An increased production of cAMP in response to catecholamines has also been observed after administration of 6-hydroxydopamine (7) or reserpine (10).Chronic exposure to acetylcholine leads to a decrease in the sensitivity of skeletal muscle to cholinergic agonists (11). Deguchi and Axelrod have shown that the sensitivity of the pineal to catecholamines is decreased after administration of isoproterenol to rats (9). This decrease has been correlated with a reduction in the number of fl-adrenergic receptors in the pineal organ (12). Furthermore, administration of isoproterenol to frogs or incubation of frog erythrocytes with isoproterenol leads to a desensitization to catecholamines, which is mediated through a decrease in receptor density (13,14).Adenylate cyclase-linked receptors for catecholamines exist in the liver where they affect carbohydrate metabolism. Administration of catecholamines leads to an increase in intracellular cAMP levels and to an increase in the rate of gluconeogenesis and glycogenolysis (15). In cat and dog liver, fl-adrenergic receptors appear to be predominantly involved in regulating these processes. However, the pharmacological specificity of adrenergic receptors in rat liver is controversial (15). It is likely that both a and fl-adrenergic receptors mediate the specific effects of catecholamines on glucose metabolism in rat liver but the exact contribution of the two types of receptors is in question (see 15). Glucocorticoids play a "permissive" role in regulating cAMP-mediated effects of hormones in liver and other organs (16,17). In adrenalectomized (Adx) rats, the stimulation of gluconeogenesis and glycogenolysis in response to catecholamines is markedly reduced (16). However, the production of cAMP in response to catecholamines is increased in Adx animals (16,18,19).Since changes in the catecholamine-sensitive adenylate cyclase occur in the absence of glucocorticoids, it was of interest to determine the number and properties of fl-adrenergic receptors in liver from normal and Adx animals.[125I]Iodohydroxybenzylpindolol (IHYP), a potent fl-receptor antagonist, has been used as the ligand in a binding assay for fl-adrenergic receptors of rat liver. The increase ...

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confidence: 99%

beta-adrenergic receptors in rat liver: effects of adrenalectomy.

Wolfe¹,

Harden²,

Molinoff³

1976

Proc. Natl. Acad. Sci. U.S.A.

135

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“…Relative fetal hepatic adenylate cyclase insensitivity to glucagon has been observed by others in liver homogenates (11,30), particles (10), and slices (10), and in vivo (10,12). This lack of response to glucagon, together with a high insulin-glucagon ratio (31), would insure glycogen storage during the last third of gestation.…”

Section: Discussionmentioning

confidence: 68%

Development of glucagon sensitivity in neonatal rat liver.

Vinicor¹,

Higdon²,

Clark³

et al. 1976

J. Clin. Invest.

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A B S T R A C T The ontogenesis of the hepatic glucagonsensitive adenylate cyclase system has been studied in the rat. With a partially purified liver membrane preparation, fetal adenylate cyclase was less responsive to glucagon than the enzyme from neonatal or adult livers.Similar results were obtained in gently prepared liver homogenates, suggesting that destruction of essential components of the fetal liver membrane did not account for the relative unresponsiveness of the adenylate cyclase enzyme to glucagon.Investigation of other factors that might account for diminished fetal hepatic responsiveness to glucagon indicate (a) minimal glucagon degradation by fetal membranes relative to 8-day or adult tissue; and (b) available adenylate cyclase enzyme, as suggested by a 13-fold increase over basal cyclic AMP formation with NaF in fetal liver membranes. These results indicate that neither enhanced glucagon degradation nor adenylate cyclase enzyme deficiency accounts for the relative insensitivity of the fetal hepatic adenylate cyclase system to glucagon.In early neonatal life, hepatic adenylate cyclase responsiveness to glucagon rapidly developed and was maximal 6 days after birth. These changes were closely paralleled by a fivefold increase in glucagon binding and the kinetically determined V.ax for cyclic AMP formation.These observations suggest that (a) fetal hepatic unresponsiveness to glucagon may be explained by a limited number of glucagon receptor sites; (b) during the neonatal period, the development of glucagon binding is expressed primarily as an increase in adenylate cyclase

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“…The membranes treated by Lubrol PX did not demonstrate any response to glucagon, however, the addition of fluoride ion resulted the same or more stimulation of adenyl cyclase activity. (Bitensky et al, 1968(Bitensky et al, , 1970 Table 3, varying concentrations of insulin did not demonstrate any inhibitory effects on glucagon stimulated adenyl cyclase activities in our preparations. Preincubation of plasma membranes with insulin had no effect.…”

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confidence: 52%