Neurochemical Research

, Volume 16, Issue 4, pp 447–451 | Cite as

β-Adrenergic receptor activity of cerebral microvessels is reduced in aged rats

  • Arshag D. Mooradian
  • Philip J. Scarpace
Original Articles


The effect of age on beta-(β) adrenergic receptor number (Bmax) and adenylate cyclase (AC) activity was determined in microvessels isolated from male F-344 rats at 3, 18, and 24 months of age. Scatchard analysis of [125I]iodocyanopindolol (ICYP) binding indicated reduced Bmax (fmol/mg) of microvessels isolated from 24 month old rats (27.2±4.9) compared with 3 month old (50.4±5.2) and 18 month old rats (p<0.01) (61.4±7.6). The basal AC activity (pmol cAMP/mg) in 24 month old rats (32.0 ±6.7) and in 18 month old rats (30.4±2.1) were significantly reduced compared to the basal activity in the young (50.1±4.2). The net isoproterenol or NaF stimulated AC activity in 24 month old rats (zero and 15.6±8.5 respectively) was also reduced compared to young rats (10.1±3.9 and 166.0±21.2 respectively). It is concluded that aging is associated with reduced isoproterenol stimulated AC activity of cerebral microvessels. This reduction is the product of reduced β-adrenergic receptor number and reduced activity of AC in aged rat cerebral microvessels.

Key Words

Aging cerebral microvessels β-adrenergic receptors 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Mooradian, A. D. 1988. Effect of aging on the blood-brain barrier. Neurobiol Aging 9:31–40.PubMedGoogle Scholar
  2. 2.
    Embree, L. J., Roubein, I. F., Jackson, D. W., and Ordway, F. 1981. Aging effect on the noradrenaline content of rat brain microvessels. Exp. Aging Res. 7:215–224.PubMedGoogle Scholar
  3. 3.
    Harik, S. I., Sharma, V. K., Wetherbee, J. R., Warren, R. H., and Banerjee, S. P. 1980. Adrenergic receptors of cerebral microvessels. Eur. J. Pharmacol. 61:207–208.PubMedGoogle Scholar
  4. 4.
    Herbst, T. J., Raichle, M. E., and Ferrendelli, J. A. 1979. β-Adrenergic regulation of adenosine-3′, 5′-monophosphate concentration in brain microvessels. Science 204:330–332.PubMedGoogle Scholar
  5. 5.
    Kobayashi, H., Frattola, L., Fetrarese, C., Spano, P. F., and Trabucchi, M. 1982. Characterization of β-adrenergic receptors in human cerebral microvessels. Neurology 32:1384–1387.PubMedGoogle Scholar
  6. 6.
    Kobayashi, H., Maoret, T., Spano, P. F., and Trabucchi, M. 1982. Effect of age on β-adrenergic receptors on cerebral microvessels. Brain Res. 244:374–377.PubMedGoogle Scholar
  7. 7.
    Nathanson, J. A., and Glaser, G. H. 1979. Identification of β-adrenergic sensitive adenylate cyclase in intracranial blood vessels. Nature (Lond.), 228:567–569.Google Scholar
  8. 8.
    Peroutka, S. K., Moskowitz, M. A., Reinhard, F., Jr., and Snyder, S. H. 1980. Neurotransmitter receptor binding in bovine cerebral microvessels. Science, 208:610–612.PubMedGoogle Scholar
  9. 9.
    Kalaria, R. N., Andorn, A. C., Tabaton, M., Whitehouse, P. J., Harik, S. I., and Unnerstall, J. R. 1989. Adrenergic receptors in aging and Alzheimer's disease: Increased β2-receptors in prefrontal cortex and hippocampus. J. Neurochem. 53:1772–1781.PubMedGoogle Scholar
  10. 10.
    Goldstein, G. W., Wolinsky, J. S., Csejtey, J. and Diamond, I. 1975. Isolation of metabolically active capillaries from rat brain. J. Neurochem. 25:715–717.PubMedGoogle Scholar
  11. 11.
    Pardridge, W. M., Eisenberg, J., and Yamada, T. 1985. Rapid sequestration and degradation of somatostatin analogues by isolated microvessels. J. Neurochem. 44:1178–1184.PubMedGoogle Scholar
  12. 12.
    Albert, Z., Orlowski, M., Azucidlo, A., and Orlowski, J. 1966. Studies on gamma-glutamyl transpeptidase activity and its histochemical localization in the central nervous system of man and different animal species. Acta. Histochem. 25:312–320.PubMedGoogle Scholar
  13. 13.
    Orlowski, M., and Meister, A. 1965. Isolation of gamma-glutamyl transpeptidase from hog kidney. J. Biol. Chem., 240:338–347.PubMedGoogle Scholar
  14. 14.
    Bessey, O. A., Lowry, O. H., and Brock, M. J. 1946. A method for the rapid determination of alkaline phosphatase with five cubic milliliters of serum. J. Biol. Chem. 164:321–329.Google Scholar
  15. 15.
    Lowry, O. H., Rosebrough, J. N., Farr, A. L., and Randall, R. J. 1951. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193:262–275.Google Scholar
  16. 16.
    Scarpace, P. J., and Yu, B. P. 1987. Diet restriction retards the age-related loss of beta-adrenergic receptors and adenylate cyclase activity in rat lung. J. Gerontol. 42:442–446.PubMedGoogle Scholar
  17. 17.
    Mooradian, A. D., Morley, J. E., and Scarpace P. J. 1988. The role of zine status in altered cardiac adenylate cyclase activity in diabetic rats. Acta. Endocrinol. 119:174–180.PubMedGoogle Scholar
  18. 18.
    Mooradian, A. D., and Scarpace, P. J. 1989. The response to isoproterenol-stimulated adenylate cyclase activity after administration ofl-triiodothyronine is reduced in aged rats. Horm. Metabol. Res. 21:638–639.Google Scholar
  19. 19.
    Mione, M. C., Dhital, K. K., Amenta, F., and Burnstock, G. 1988. An increase in the expression of neuropeptidergic vasodilator, but not vasoconstrictor, cerebrovascular nerves in aging rats. Brain Res. 460:103–113.PubMedGoogle Scholar
  20. 20.
    Saba, H., Cowen, T., Haven, A. J., and Burnstock, G. 1984. Reduction in noradrenergic perivascular nerve density in the left and right cerebral arteries of old rabbits. J. Cereb. Blood Flow Metab. 4:284–389.PubMedGoogle Scholar
  21. 21.
    Edvinsson, L., Lindvall, M., Neilsen, K. C., and Owman C. H. 1973. Are brain vessels innervated also by central (non-sympathetic) adrenergic neurons? Brain Res. 63:496–499.PubMedGoogle Scholar
  22. 22.
    Itakura, T., Yamamoto, K., Tohyama, M., and Shimizu, N. 1977. Central dual innervation of arterioles and capillaries in the brain. Stroke 8:360–365.PubMedGoogle Scholar
  23. 23.
    McDonald, D. M., and Rasmussen, G. L. 1977. An ultrastructural analysis of neurites in the basal lamina of capillaries in the chinchilla cochlear nucleus. J. Comp. Neurol. 173:475–496.PubMedGoogle Scholar
  24. 24.
    Rennels, M., and Nelson, E. 1975. Capillary innervation in the mammalian central nervous system. An electron microscopic demonstration. Am. J. Anatomy 144:233–241.Google Scholar
  25. 25.
    Scarpace, P. J., and Abrass, I. B. 1988. Alpha-and beta-adrenergic receptor function in the brain during senescence. Neurobiol. Aging 9:53–58.PubMedGoogle Scholar
  26. 26.
    Scarpace, P. J. 1986. Decreased beta-adrenergic responsiveness during senescence. Federation Proc. 45:51–54.Google Scholar
  27. 27.
    Robberecht, P., Gillard, M., Waelbroeck, M., Camus, J-C., DeNeef, P., and Christophe, J. 1986. Decreased stimulation of adenylate cyclase by growth hormone releasing factor in the anterior pituitary. Neuroendocrinology 44:429–432.PubMedGoogle Scholar
  28. 28.
    Mooradian A. D. 1990. Age-related differences in body weight loss in response to altered thyroidal status. Exp. Gerontol. 25:29–35.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1991

Authors and Affiliations

  • Arshag D. Mooradian
    • 1
  • Philip J. Scarpace
    • 2
  1. 1.Tucson DVA Medical Center and Department of MedicineUniversity of Arizona College of MedicineTucson
  2. 2.GRECC, Gainsville DVA Medical Center, Department of PharmacologyUniversity of FloridaGainsville

Personalised recommendations