Evidence for adenylate cyclase-coupled A1-adenosine receptors on ventricular cardiomyocytes from adult rat and dog heart |
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| Authors: | M Henrich H M Piper J Schrader |
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| Institution: | 1. Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Boston, MA, USA;2. Division of Palliative Medicine, Brigham and Women’s Hospital, Boston, MA, USA;3. Harvard Medical School, Boston, MA, USA;4. Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT), Durham VA Health Care System, NC, USA;5. Department of Population Health Sciences Duke University, Durham, NC, USA;6. Center for the Study of Aging and Human Development Duke University, Durham, NC, USA;7. Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University School of Medicine, Durham, NC, USA;8. Cancer Control and Population Sciences, Duke Cancer Institute, Durham, NC, USA;9. Department of Sociology, Duke University, Durham, NC, USA;10. Department of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USA;1. Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University College of Medicine, Taoyuan, Taiwan;2. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan;3. Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan;4. School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan;5. Department of Emergency Medicine, Chang Gung Memorial Hospital, Chiayi Branch and Chang Gung University College of Medicine, Taoyuan, Taiwan;1. Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California;2. Department of Obstetrics and Gynecology, Hacettepe University School of Medicine, Sihhiye, Ankara, Turkey;3. Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China;1. Unidad de Amiloidosis y Mieloma, Servicio de Hematología, Hospital Clínic de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, España;2. Servicio de Dermatología, Hospital Clínic de Barcelona, Barcelona, España;3. Servicio de Inmunología, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, España |
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| Abstract: | Isolated metabolically stable cardiomyocytes from adult rats and mongrel dogs were used to characterize the mechanism underlying the antiadrenergic effect of adenosine. In a system not affected by cellular heterogeneity, isoproterenol (3 x 10(-9) M - 10(-5) M) in the presence of adenosine deaminase (5U/ml) dose dependently increased cellular cAMP (5-80 pmol/mg). The effect of isoproterenol (0.1 microM) was inhibited by various adenosine derivatives, the rank order of potency being in the rat: (-)-N6-(R-phenyl-isopropyl)-adenosine (R-PIA) greater than 5'-N-ethylcarboxamidoadenosine (NECA) greater than S-PIA, and in the dog NECA greater than R-PIA greater than S-PIA. The cAMP increase induced by forskolin (1 microM) was attenuated in the rat by R-PIA. 8-phenyltheophylline (3 microM) antagonized the effect of R-PIA on isoproterenol-stimulated cAMP formation. Basal cAMP content was not influenced by R-PIA or NECA. Omission of adenosine deaminase from the incubation medium attenuated the isoproterenol-induced cAMP increase in the rat by about 30%. Our findings provide evidence for the presence of adenylate cyclase-coupled A1-adenosine receptors on cardiomyocytes which may mediate the antiadrenergic effect of adenosine in the heart. |
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