Stimulation of beta-adrenoceptors inhibits calcium-dependent potassium-channels in mouse macrophages

Journal Article · Mon Dec 01 04:00:00 EST 1986 · J. Cell. Physiol.; (United States)

DOI:https://doi.org/10.1002/jcp.1041290307· OSTI ID:6521195

Rosati, C; Hannaert, P; Dausse, J P; Braquet, P; Garay, R

K/sup +/ efflux in mouse macrophages exhibited a rate constant (k/sub k/) of 0.67 +/- 0.04 (h)/sup -1/. This was strongly stimulated by increasing concentrations of the Ca/sup 2 +/ ionophore A23187 up to a maximal value of 4.01 +/- 0.25 (h)/sup -1/ with an IC/sub 50/ of 7.6 +/- 1.9 ..mu..M. Similar results were obtained with the Ca/sup 2 +/ ionophore ionomycin. Binding experiments with /sup 3/H-dihydroalprenolol revealed a high density of beta-adrenergic receptors with apparent dissociation constant of 2.03 +/- 0.06 nM. Isoproterenol at a concentration of 10/sup -6/ -10/sup -5/ M induced a two- to threefold stimulation of endogenous levels of cyclic AMP (cAMP). A23187-stimulated K/sup +/ efflux was partially inhibited by (i) stimulation of adenylate cyclase with isoproterenol, forskolin or, PGE/sub 1/; (ii) exogenous cAMP; and (iii) inhibition of phosphodiesterase with MIX (1-methyl-3-isobutylxanthine). Maximal inhibition of K/sup +/ efflux was obtained by simultaneous addition of isoproterenol and MIX. In dose-response curves, the isoproterenol-sensitive K/sup +/ efflux was half-maximally inhibited (IC/sub 50/) with 2-5 x 10/sup -10/ M of isoproterenol concentration. Propranolol was able to completely block the effect of isoproterenol, with an IC/sub 50/ of about 1-2 x 10/sup -7/ M. Isoproterenol and MIX did not inhibit A23187-stimulated K/sup +/ efflux in an incubation medium where NaCl was replaced by sucrose (or choline), suggesting the involvement of an Na/sup +/:Ca/sup 2 +/ exchange mechanism. The results show that stimulation of beta-adrenoceptors in mouse macrophages counter balances the opening of K/sup +/ channels induced by the calcium ionophore A23187. This likely reflects a decrease in cytoslic free calcium content via a cAMP-mediated stimulation of Na/sup +/:Ca/sup 2 +/ exchange.

• Research Organization: INSERM U7, Paris, France
• OSTI ID: 6521195
• Journal Information: J. Cell. Physiol.; (United States), Journal Name: J. Cell. Physiol.; (United States) Vol. 129:3; ISSN JCLLA
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
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ANIMALS
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IODINE ISOTOPES
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ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
MACROPHAGES
MAMMALS
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
MICE
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PHAGOCYTES
POTASSIUM CHLORIDES
POTASSIUM COMPOUNDS
PROSTAGLANDINS
PROTEINS
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNOLOGY
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES