Desensitization of beta-adrenergic responses in adipocytes involves receptor subtypes and cAMP phosphodiesterase. 1995

A Bousquet-Mélou, and J Galitzky, and C M Moreno, and M Berlan, and M Lafontan
Institut National de la Santé et de la Recherche Médicale Unité 317, Faculté de Médicine, Université Paul Sabatier, Toulouse, France.

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.

UI MeSH Term Description Entries
D007545 Isoproterenol Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D008066 Lipolysis The metabolic process of breaking down LIPIDS to release FREE FATTY ACIDS, the major oxidative fuel for the body. Lipolysis may involve dietary lipids in the DIGESTIVE TRACT, circulating lipids in the BLOOD, and stored lipids in the ADIPOSE TISSUE or the LIVER. A number of enzymes are involved in such lipid hydrolysis, such as LIPASE and LIPOPROTEIN LIPASE from various tissues. Lipolyses
D008297 Male Males
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010727 Phosphoric Diester Hydrolases A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4. Phosphodiesterase,Phosphodiesterases,Hydrolases, Phosphoric Diester
D011943 Receptors, Adrenergic, beta One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS. Adrenergic beta-Receptor,Adrenergic beta-Receptors,Receptors, beta-Adrenergic,beta Adrenergic Receptor,beta-Adrenergic Receptor,beta-Adrenergic Receptors,Receptor, Adrenergic, beta,Adrenergic Receptor, beta,Adrenergic beta Receptor,Adrenergic beta Receptors,Receptor, beta Adrenergic,Receptor, beta-Adrenergic,Receptors, beta Adrenergic,beta Adrenergic Receptors,beta-Receptor, Adrenergic,beta-Receptors, Adrenergic
D004280 Dobutamine A catecholamine derivative with specificity for BETA-1 ADRENERGIC RECEPTORS. It is commonly used as a cardiotonic agent after CARDIAC SURGERY and during DOBUTAMINE STRESS ECHOCARDIOGRAPHY. Dobucor,Dobuject,Dobutamin Fresenius,Dobutamin Hexal,Dobutamin Solvay,Dobutamin-ratiopharm,Dobutamina Inibsa,Dobutamina Rovi,Dobutamine (+)-Isomer,Dobutamine Hydrobromide,Dobutamine Hydrochloride,Dobutamine Lactobionate,Dobutamine Phosphate (1:1) Salt, (-)-Isomer,Dobutamine Tartrate,Dobutamine Tartrate (1:1), (R-(R*,R*))-Isomer,Dobutamine Tartrate (1:1), (S-(R*,R*))-Isomer,Dobutamine, (-)-Isomer,Dobutamine, Phosphate (1:1) Salt (+)-Isomer,Dobutrex,Lilly 81929,Oxiken,Posiject,Dobutamin ratiopharm,Hydrobromide, Dobutamine,Hydrochloride, Dobutamine,Lactobionate, Dobutamine,Tartrate, Dobutamine
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005576 Colforsin Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. Coleonol,Forskolin,N,N-Dimethyl-beta-alanine-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho(2,1-b)pyran-6-yl Ester HCl,NKH 477,NKH-477,NKH477
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic

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