β2-Adrenergic receptor-stimulated increase in cAMP in rat heart cells is not coupled to changes in Ca2+ dynamics, contractility, or phospholamban phosphorylation

R. P. Xiao, C. Hohl, R. Altschuld, L. Jones, B. Livingston, B. Ziman, B. Tantini, E. G. Lakatta

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Abstract

Previous studies have shown that both β1- and β2-adrenergic receptors (AR) are present in rat ventricular myocytes, but stimulation of these receptor subtypes elicits qualitatively different cellular responses (Xiao, R.-P., and Lakatta, E. G. (1993) Circ. Res. 73, 286-300). In the present study, the biochemical mechanism underlying the distinct βAR subtype actions have been investigated. Although both β1AR and β2AR stimulation increased total cellular cAMP in suspensions of rat ventricular myocytes to a similar extent, the maximum elevation of the membrane bound cAMP by β2AR stimulation was only half of that induced by β1AR stimulation, suggesting that stimulation the βAR subtypes leads to different compartmentation of cAMP. The effects of β1AR stimulation on Ca2+ transient (indexed by the transient increase in indo-1 fluorescence ration after excitation) and contraction amplitude (measured via photodiode array) and their kinetics closely paralleled the increase in cAMP. In contrast, the increase in both membrane bound and total cAMP content after β2AR stimulation were completely dissociated from the effects of β2AR stimulation to increase the amplitudes of cytosolic Ca2+ transient and contraction. Furthermore, β2AR stimulation did not phosphorylate phospholamban to the same extent as did β1AR stimulation. This finding provides a mechanism for the failure of β2AR stimulation to accelerate the kinetics of the Ca2+i, (cytosolic Ca2+) transient and contraction. These results indicate that the effects of β2AR stimulation on Ca2+, transient and contraction are uncoupled from the cAMP production and cAMP-dependent protein phosphorylation and indicate that, in addition to coupling to adenylate cyclase, β2AR stimulation also activates other signal transduction pathway(s) to produce changes in cytosolic Ca2+ and contraction.

Original languageEnglish (US)
Pages (from-to)19151-19156
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number29
StatePublished - Jan 1 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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