DESENSITIZATION OF BETA-ADRENERGIC RESPONSES IN ADIPOCYTES INVOLVES RECEPTOR SUBTYPES AND CAMP-PHOSPHODIESTERASE

被引：17

作者：

BOUSQUETMELOU, A ^{[1
]}

GALITZKY, J ^{[1
]}

MORENO, CM ^{[1
]}

BERLAN, M ^{[1
]}

LAFONTAN, M ^{[1
]}

机构：

[1] INST LOUIS BUGNARD,F-31054 TOULOUSE,FRANCE

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION | 1995年 / 289卷 / 02期

关键词：

DESENSITIZATION; BETA-ADRENOCEPTOR AGONISTS; ADIPOCYTE; PHOSPHODIESTERASE; BETA-ADRENOCEPTOR SUBTYPES; LIPOLYSIS;

D O I：

10.1016/0922-4106(95)90100-0

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Acute exposure of isolated adipocytes to isoproterenol induces the desensitization of lipolytic responses to norepinephrine and selective beta(1)-, beta(2)- and beta(3)-adrenoceptor agonists, as well as the adrenocorticotropic hormone 1-24 fragment (ACTH). Forskolin and 8-bromo-cAMP responses are also desensitized. When lipolysis was measured in the presence of OPC 3911 {N-cyclohexyl-N-2-hydroxyethyl-4(6-(1,2-dihydro-2-oxoquinolyloxy))butyramide}, a specific inhibitor of the cAMP phosphodiesterase of adipocytes, the desensitization of all lipolytic agents - except the beta(2)-adrenoceptor agonist - was abolished. Isoproterenol induced a similar loss (35%) of both membrane beta(1)- and beta(2)-adrenoceptors and an uncoupling of beta(1)-adrenoceptors, but did not modify the weak coupling of control beta(2)-adrenoceptors. These data suggest that isoproterenol induced (i) an activation of the cAMP phosphodiesterase, which is solely responsible for the desensitization of norepinephrine response as well as beta(1)- and beta(3)-adrenoceptor mediated responses and (ii) an additional desensitization of the sole beta(2)-adrenergic signaling system which suggests a subtype-selective pattern of regulating processes.

引用

页码：235 / 247

页数：13

共 51 条

[1] Beebe, Redmon, Blackmore, Corbin, Discriminative insulin antagonism of stimulatory effects of various cAMP analogs on adipocyte lipolysis and hepatocyte glycogenolysis, J. Biol. Chem., 260, (1985)
[2] Bousquet-Melou, Galitzky, Carpene, Lafontan, Berlan, β-adrenergic control of lipolysis in primate white fat cells comparative study with non-primate mammals, Am J Physiol, 267, (1994)
[3] Burns, Langley, Terry, Bylund, Studies on desensitization of adrenergic receptors of human adipocytes, Metabolism, 31, (1982)
[4] Carpene, Ambid, Lafontan, Predominance of β3-adrenergic component in catecholamine activation of lipolysis in garden dormouse adipocytes, Am J Physiol, 266, (1994)
[5] Carpene, Castan, Collon, Galitzky, Moratinos, Lafontan, Adrenergic lipolysis in guinea pig is not a β3-adrenergic response comparison with human adipocytes, Am J Physiol, 266, (1994)
[6] Carpene, Galitzky, Collon, Escalpez, Dauzats, Lafontan, Desensitization of beta-1 and beta-2, but not beta-3, adrenoceptor-mediated lipolytic responses of adipocytes after long-term norepinephrine infusion, J. Pharmacol. Exp. Ther., 265, (1993)
[7] Crampes, Beauville, Riviere, Guarrigues, Lafontan, Lack of desensitization of catecholamine-induced lipolysis in fat cells from trained and sedentary women after physical exercise, J. Clin. Endocrin. Metab., 67, (1988)
[8] Degerman, Smith, Tornqvist, Vasta, Belfrage, Manganiello, Evidence that insulin and isoprenaline activate the cGMP-inhibited low-Km cAMP phosphodiesterase in rat fat cells by phosphorylation, Proc. Natl. Acad. Sci. USA, 87, (1990)
[9] Dole, Meinertz, Microdetermination of long chain fatty acids in plasma and tissues, J. Biol. Chem., 235, (1960)
[10] Gettys, Blackmore, Redmon, Beebe, Corbin, Short-term feedback regulation of cAMP by accelerated degradation in rat tissues, J. Biol. Chem., 262, (1987)

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