Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 331, Issue 1, pp 71–75

Uncoupling between beta-adrenoceptors and adenylate cyclase in dog ischemic myocardium

  • C. Devos
  • P. Robberecht
  • P. Nokin
  • M. Waelbroeck
  • M. Clinet
  • J. C. Camus
  • P. Beaufort
  • P. Schoenfeld
  • J. Christophe
Article

Summary

We evaluated the effects of ischemic injury on the myocardial adenylate cyclase system, 5 h after ligation of the left anterior descending coronary in 5 anesthetized dogs. Crude cardiac membrane preparations were isolated from control and ischemic areas of ventricular myocardium and tested for: 1. L-(125I)iodocyanopindolol binding, in the absence and presence of ±-isoprenaline and GTP, and 2. adenylate cyclase activity. The density of beta-adrenoceptors increased by 35% in membranes from ischemic areas while the proportion of receptors in a high affinity state for ±-isoprenaline decreased from 43% to 20%. Adenylate cyclase activities in the basal state and under stimulation with NaF, forskolin, Gpp(NH)p, ±-isoprenaline and VIP were all markedly and similarly reduced, being only about 30% of comparable activities in membranes from control areas. The ±-isoprenaline subsensitivity of cardiac adenylate cyclase can, thus, be attributed to a defective enzymatic system and not to a reduction in the number of beta-adrenoceptors implying that the internal components of the system were more sensitive to acute ischemia than the outward oriented hormone receptors. It is tempting to ascribe this uncoupling to a functional depletion in the guanine nucleotide-binding regulatory protein Ns that might reflect a loss of high energy phosphate stores including GTP.

Key words

Dog heart Beta-adrenoceptors Adenylate cyclase Heart ischemia 

Abbreviations

CYP

cyanopindolol

Gpp(NH)p

5′-guanyl imidodiphosphate

VIP

vasoactive intestinal peptide

Ns

guanine nucleotide-binding regulatory protein

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Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • C. Devos
    • 1
  • P. Robberecht
    • 2
  • P. Nokin
    • 1
  • M. Waelbroeck
    • 2
  • M. Clinet
    • 1
  • J. C. Camus
    • 2
  • P. Beaufort
    • 1
  • P. Schoenfeld
    • 1
  • J. Christophe
    • 2
  1. 1.Sanofi, Labaz-Sanofi Research CenterBrusselsBelgium
  2. 2.Department of Biochemistry and Nutrition, Medical SchoolUniversité Libre de BruxellesBrusselsBelgium

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