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

Journal Article · Mon Dec 01 00:00:00 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), Vol. 129:3
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
AMP
RADIOIMMUNOASSAY
MEMBRANE TRANSPORT
BIOCHEMICAL REACTION KINETICS
POTASSIUM CHLORIDES
CALCIUM CHLORIDES
INHIBITION
IODINE 125
IONS
MACROPHAGES
MICE
PROSTAGLANDINS
RECEPTORS
TRITIUM COMPOUNDS
ALKALI METAL COMPOUNDS
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
CALCIUM COMPOUNDS
CALCIUM HALIDES
CHARGED PARTICLES
CHLORIDES
CHLORINE COMPOUNDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
HALIDES
HALOGEN COMPOUNDS
IMMUNOASSAY
IMMUNOLOGY
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PHAGOCYTES
POTASSIUM COMPOUNDS
PROTEINS
RADIOASSAY
RADIOIMMUNOLOGY
RADIOISOTOPES
REACTION KINETICS
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics