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Changes in cAMP formation in mononuclear leukocytes of heart and renal transplant recipients

Research in Experimental Medicine volume 194, pages 81–96 (1994)Cite this article

Abstract

In mononuclear leukocytes (MNL) of renal transplant recipients treated with cyclosporine A and prednisone, an increase of basal cAMP generation has been observed. In order to characterize the mechanisms underlying changes of cAMP generation in patients who were treated with immunosuppressives following heart transplantation, we investigated the β-adrenoceptor—G protein—adenylate cyclase signal transduction cascade in heart transplant recipients and for comparison in renal transplant recipients as well as controls. Basal cAMP formation in MNL was elevated in heart transplant recipients by 27% and in renal transplant recipients by 148% compared to controls. Following β-adrenoceptor stimulation with isoprenaline, cAMP formation in MNL of heart transplant recipients was similar to the controls, but was enhanced in renal transplant recipients to 138%. Investigation of β-adrenoceptor density on MNL as a possible cause for increased cAMP formation revealed similar receptor numbers in controls and in cardiac or renal transplant recipients. Furthermore, the increase of the β-adrenoceptor density on MNL, which is observed following infusion of isoprenaline, was similar in controls and heart transplant recipients. The amount of pertussis- and cholera toxin substrates was the same in heart transplant recipients as in controls. In contrast, MNL of renal transplant recipients showed a marked increase of Gsα by 45% and a smaller albeit significant increase of G1α by 15%, as judged by cholera toxin and pertussis toxin labeling, respectively. Investigation of inotropic parameters by echocardiography under control conditions and during the infusion of increasing concentrations of isoprenaline revealed no difference in the basal contractility and the inotropic response to β-adrenergic stimulation in controls and heart transplant recipients. It is concluded that changes of G-protein expression are involved in the increase of the cAMP-generation in MNL of heart transplant recipients. These alterations in MNL cannot be taken as a model of cellular function in the transplanted heart, but it is reasonable to suggest that elevations of cAMP formation in MNL may contribute to the immunosuppressive effects of the treatment with cyclosporine A or corticosteroids, the mechanism of which could be an alteration of Gsα or the catalyst in renal transplant recipients and the catalyst in heart transplant recipients which occurs without any changes of β-adrenoceptors.

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Abbreviations

SDS-PAGE :

sodiumdodecylsulfate polyacrylamide gel electrophoresis

EDD :

enddiastolic left ventricular diameter

ESD :

endsystolic left vertricular diameter

FS :

fractional shortening

P/D :

pressure-dimension-ratio

HTR :

heart transplant recipients

RTR :

renal transplant recipients

G protein :

GTP-binding protein

G sα :

α subunit of stimulatory G protein

G iα :

α subunit of inhibitory G protein

T s/c :

T suppressor/cytotoxic lymphocytes (also: T8)

T h :

T helper lymphocytes (also T4)

125 I-Cyp :

[125I]Iodocyanopindolol

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Affiliations

  1. Klinik III für Innnere Medizin der Universität zu Köln, Joseph-Stelzmann-Strasse 9, D-50924, Cologne, Germany

    Herbert Lensche, Frank Diet, Erland Erdmann & Michael Böhm

  2. Herzchirurgische Klinik, Klinikum Großhadern, Marchioninistrasse 15, D-81377, Munich, Germany

    Peter Überfuhr & Bruno Reichart

  3. Medizinische Klinik 1, Klinikum Großhadern, Marchioninistrasse 15, D-81377, Munich, Germany

    Wolfgang von Scheidt

Authors
  1. Herbert Lensche
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  2. Frank Diet
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  3. Wolfgang von Scheidt
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  4. Peter Überfuhr
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  5. Bruno Reichart
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  6. Erland Erdmann
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  7. Michael Böhm
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Lensche, H., Diet, F., von Scheidt, W. et al. Changes in cAMP formation in mononuclear leukocytes of heart and renal transplant recipients. Res. Exp. Med. 194, 81–96 (1994). https://doi.org/10.1007/BF02576369

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  • DOI: https://doi.org/10.1007/BF02576369

Key words

  • Heart transplantation
  • Renal transplantation
  • G proteins
  • cAMP
  • Adenylate cyclase