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

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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.

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Abbreviations

CYP:

cyanopindolol

Gpp(NH)p:

5′-guanyl imidodiphosphate

VIP:

vasoactive intestinal peptide

Ns:

guanine nucleotide-binding regulatory protein

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Authors and Affiliations

  1. Sanofi, Labaz-Sanofi Research Center, 1, Av. de Béjar, B-1120, Brussels, Belgium

    C. Devos, P. Nokin, M. Clinet, P. Beaufort & P. Schoenfeld

  2. Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, 115, Boulevard de Waterloo, B-1000, Brussels, Belgium

    P. Robberecht, M. Waelbroeck, J. C. Camus & J. Christophe

Authors
  1. C. Devos
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  2. P. Robberecht
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  3. P. Nokin
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  4. M. Waelbroeck
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  5. M. Clinet
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  6. J. C. Camus
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  7. P. Beaufort
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  8. P. Schoenfeld
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  9. J. Christophe
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Devos, C., Robberecht, P., Nokin, P. et al. Uncoupling between beta-adrenoceptors and adenylate cyclase in dog ischemic myocardium. Naunyn-Schmiedeberg's Arch. Pharmacol. 331, 71–75 (1985). https://doi.org/10.1007/BF00498853

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  • DOI: https://doi.org/10.1007/BF00498853

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