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Norepinephrine-induced Na+ influx in brown adipocytes is cyclic AMP-mediated
The Wenner-Gren Institute, University of Stockholm, Stockholm, Sweden.
The Wenner-Gren Institute, University of Stockholm, Stockholm, Sweden.ORCID-id: 0000-0001-8889-5803
The Wenner-Gren Institute, University of Stockholm, Stockholm, Sweden.
1986 (Engelska)Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 261, nr 31, s. 14377-14385Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

To examine the involvement of Na+ ions in adrenergic responses in brown adipose tissue, a method is described for measuring Na+ influx into isolated brown adipocytes, using short (30 s) incubations with 22Na+, followed by a two-step centrifugation recovery procedure. Using this method, a clear norepinephrine-stimulated accumulation of intracellular 22Na+ was observed, which was enhanced by the addition of ouabain, was insensitive to amiloride (a Na+/H+ exchange blocker), and could not be mimicked by the total removal of oxygen from the incubation medium. The norepinephrine-stimulated Na+ influx was dose-dependent for the hormone with an EC50 of 250 nM, was blocked by the beta-antagonist propranolol but not by the alpha 1-antagonist prazosin, and could be induced by adrenergic agonists with the order of potency: isoproterenol greater than norepinephrine greater than phenylephrine, indicating a beta-receptor-mediated process. The Na+ influx was found to be cAMP-dependent since it could be induced by both theophylline (a phosphodiesterase inhibitor) and forskolin (an adenylate cyclase activator), but it was independent of other known cellular cAMP-dependent responses since neither addition of fatty acid substrates (octanoate or palmitate), nor of the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone could induce the phenomenon, despite having significant stimulatory effects on cellular respiration. Furthermore, total respiratory inhibition with rotenone, or total oxygen depletion of the medium with dithionite, did not prevent the normal norepinephrine-induced Na+ influx. The possibility that this beta-mediated norepinephrine-stimulated Na+ influx plays an important physiological role in brown adipose tissue activity is discussed, perhaps as one of the, as yet undefined, signals initiating tissue growth in the chronically beta-stimulated tissue of animals facing long-term increases in thermogenic demands.

Ort, förlag, år, upplaga, sidor
American Society for Biochemistry and Molecular Biology, 1986. Vol. 261, nr 31, s. 14377-14385
Nationell ämneskategori
Medicin och hälsovetenskap Farmakologi och toxikologi
Identifikatorer
URN: urn:nbn:se:oru:diva-79022ISI: A1986E668100005PubMedID: 3021738Scopus ID: 2-s2.0-0022839238OAI: oai:DiVA.org:oru-79022DiVA, id: diva2:1386349
Forskningsfinansiär
Wenner-Gren Stiftelserna
Anmärkning

This work was supported by a personal grant from the Wenner- Grenska Samfundet (to E. C.), by a grant from the Swedish Natural Science Research Council (to Barbara Cannon and J. N.), and by a grant from the Swedish Cancer Research Council (to J. N.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "aduer- tisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Tillgänglig från: 2013-10-21 Skapad: 2020-01-17 Senast uppdaterad: 2020-01-24Bibliografiskt granskad

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