Age-related change in adrenergic regulation of glycogen phosphorylase in rat hepatocytes

Tsujimoto, Aiko; Tsujimoto, Gozoh; Hoffman, Brian B.

doi:10.1016/0047-6374(86)90025-4

Cited by 8 publications

(5 citation statements)

References 18 publications

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“…Our results suggest that these sites within the glucagon signaling pathway are important in the age-and training-induced changes in hepatic glucose production previously observed. In the old animals, GppNHp and AlF stimulation of AC was compromised to nearly the same extent as forskolin, suggesting that changes in AC protein content (and by implication, protein expression), AC integrity or enzymatic function, and/or AC isoform expression may be contributing factors to this apparent lesion at AC (43). There may also be molecular interactions downstream from cAMP that help elucidate alterations in the hormonal signaling cascade in aging rat liver.…”

Section: Discussionmentioning

confidence: 99%

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Attenuation of age-related declines in glucagon-mediated signal transduction in rat liver by exercise training

Podolin

Wills

Wood

et al. 2001

American Journal of Physiology-Endocrinology and Metabolism

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This study investigated alterations in glucagon receptor-mediated signal transduction in rat livers from 7- to 25-mo-old animals and examined the effects of exercise training on ameliorating these changes. Sixty-six young (4 mo), middle-aged (12 mo), and old (22 mo) male Fischer 344 rats were divided into sedentary and trained (treadmill running) groups. Isolated hepatic membranes were combined with [(125)I-Tyr(10)]monoiodoglucagon and nine concentrations of glucagon to determine maximal binding capacity (B(max)) and dissociation constant (K(d)). No alterations were found in B(max) among groups; however, middle-aged trained animals had significantly higher glucagon affinity (lower K(d); 21.1 +/- 1.8 nM) than did their untrained counterparts (50.2 +/- 7.1 nM). Second messenger studies were performed by measuring adenylyl cyclase (AC) specific activity under basal conditions and with four pharmacological stimulations to assess changes in receptor-dependent, G protein-dependent, and AC catalyst-dependent cAMP production. Age-related declines were observed in the old animals under all five conditions. Training resulted in increased cAMP production in the old animals when AC was directly stimulated by forskolin. Stimulatory G protein (G(s)) content was reduced with age in the sedentary group; however, training offset this decline. We conclude that age-related declines in glucagon signaling capacity and responsiveness may be attributed, in part, to declines in intrinsic AC activity and changes in G protein [inhibitory G protein (G(i))/G(s)] ratios. These age-related changes occur in the absence of alterations in glucagon receptor content and appear to involve both G protein- and AC-related changes. Endurance training was able to significantly offset these declines through restoration of the G(i)/G(s) ratio and AC activity.

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Section: Discussionmentioning

confidence: 99%

“…The ability of glucagon to stimulate hepatic glycogenolysis has been found to either decrease (43) or remain unchanged (16) with increasing age. Aging has also been shown to dramatically impair hepatic gluconeogenic capacity; specifically, our laboratory and others (24,31,32) have found age-related declines in glucagon-stimulated hepatic gluconeogenesis.…”

mentioning

confidence: 99%

Attenuation of age-related declines in glucagon-mediated signal transduction in rat liver by exercise training

Podolin

Wills

Wood

et al. 2001

American Journal of Physiology-Endocrinology and Metabolism

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“…In neonatal and very young rats, catecholamines activate glycogen phosphorylase mainly via beta-receptors (Sherline et al, 1974), whereas alpha-1 receptors are relatively inactive. However, as rats age, the number of beta-receptors expressed in the hepatocytes declines markedly (McMillian et al, 1983) and alpha-1 adrenergic receptor-mediated effects predominate (Blair et al, 1979a, b;Tsujimoto et al, 1986a). In female rats, beta-adrenergic receptor-mediated responses are apparently better preserved (Studer and Borle, 1982).…”

Section: Regulation Of Alpha-l Adrenergic Receptors In Livermentioning

confidence: 99%

The alpha-1 Adrenergic Receptors

Ruffolo¹

1987

The Receptors

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All rights reservedNo part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher.Preface vii ology will allow alpha-l adrenergic receptors to be isolated and purified and their amino acid sequence to be identified. This will ultimately allow for the systematic subclassification of alpha-l adrenergic receptors and for their differential regulation to be studied in greater detail. These new advances are likely to take place within the next five years, and it is our intent for this review of alpha-l adrenergic receptor pharmacology to provide an accurate summary of the current state of knowledge relating to alpha-l adrenergic receptors, which we hope will serve as a foundation upon which to build a broader base of knowledge in the future.

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“…[3H]Prazosin binding experiments were performed on a crude cellular homogenate as previously described (32). Saturation binding experiments with [3H]prazosin were carried out at a range of 0.5-5 nM.…”

Section: Fractional Inactivation Ofalpha Receptors By Phenoxybenzaminementioning

confidence: 99%

In vivo desensitization of glycogenolysis to Ca2+-mobilizing hormones in rat liver cells.

Tsujimoto¹,

Tsujimoto²,

Kato³

et al. 1988

J. Clin. Invest.

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Rat hepatocytes contain several types of Ca2`-linked receptors, all of which stimulate glycogen breakdown by increasing cytosolic free Ca2" concentration ([Ca2+jc). In vivo desensitization of this Ca2" messenger system was studied in hepatocytes isolated from either pheochromocytoma (PHEO)-harboring and chronically norepinephrine (NE)-infused rats. Homologous desensitization for alpha,-adrenergic receptor-mediated phosphorylase activation developed in the early stage of PHEO rats (3-4 wk after implantation), whereas, in the later stage of tumor development or in the NE-infused rats, phosphorylase responses to all Ca2+-mobilizing stimulations were subsensitive (heterologous desensitization). In the homologous desensitization, the [Ca2"Ic response to alpha,-adrenergic stimulation was selectively reduced. We found, using the phenoxybenzamine inactivation method, that there was a linear relationship between alpha, receptor density and the [Ca2"ic response; consequently, the blunted [Ca2"jc response to alpha,-adrenergic stimulation could not be explained by the 34% downregulation of alpha, receptors seen in these rats.These results indicated that uncoupling at a step proximal to alpha, receptor-stimulated [Ca2"Jc increase is also of primary importance in homologous desensitization of phosphorylase activation. On the other hand, heterologous desensitization also involved alteration(s) at steps distal to the rise in [Ca2"Ic.Our data demonstrate that prolonged exposure to catecholamines results in desensitization of the [Ca2+Jc mobilization pathway and may involve multiple mechanisms.

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Age-related change in adrenergic regulation of glycogen phosphorylase in rat hepatocytes

Cited by 8 publications

References 18 publications

Attenuation of age-related declines in glucagon-mediated signal transduction in rat liver by exercise training

Attenuation of age-related declines in glucagon-mediated signal transduction in rat liver by exercise training

The alpha-1 Adrenergic Receptors

In vivo desensitization of glycogenolysis to Ca2+-mobilizing hormones in rat liver cells.

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