Abstract
Many hormones interact with receptors which stimulate the enzyme adenylate cyclase. Less well characterized are those receptors which mediate an inhibition of adenylate cyclase activity1. However, guanine nucleotides are clearly important in the regulation of both stimulatory and inhibitory receptors2. Monovalent cations, notably Na+, regulate many inhibitory receptor systems but apparently not stimulatory receptors1. We investigate here the effects of Na+ and guanine nucleotides on the adenylate cyclase-coupled inhibitory α2-adrenergic receptor of the rabbit platelet3. Computer modelling of adrenaline competition curves with 3H-dihydroergocryptine (3H-DHE) indicates that adrenaline induces two distinct affinity states of the α2 receptor—one of higher (α2H) and the other of lower (α2L) affinity. Guanyl-5′-yl-imidodiphosphate (Gpp(NH)p) seems to reduce adrenaline affinity by converting the high-affinity state into the low-affinity form of the receptor. In contrast, Na+ reduces adrenaline affinity at both the high- and low-affinity states of the α2 receptor while preserving receptor heterogeneity. Thus, guanine nucleotides and Na+ differ in the manner by which each reduces agonist affinity for the α2-adrenergic receptor.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Jakobs, K. H. Molec. cell. Endocr. 16, 147–156 (1979).
Rodbell, M. Nature 284, 17–22 (1980).
Harwood, J. P., Moskowitz, J. & Krishna, G. Biochem. biophys. Acta 261, 444–456 (1972).
Hoffman, B. B., De Lean, A., Wood, C. L., Schocken, D. D. & Lefkowitz, R. J. Life Sci. 24, 1739–1746 (1979).
Hoffman, B. B., Mullikin-Kilpatrick, D. & Lefkowitz, R. J. J. biol. Chem. 255, 4645–4652 (1980).
Kent, R. S., De Lean, A. & Lefkowitz, R. J. Molec. Pharmac. 17, 14–23 (1980).
Tsai, B. S. & Lefkowitz, R. J. Molec. Pharmac. 14, 540–548 (1978).
Blume, A. J. Proc. natn. Acad. Sci. U.S.A. 75, 1713–1717 (1978).
Rosenberger, L. B., Yamamura, H. I. & Roeske, W. R. J. biol. Chem. 255, 820–823 (1980).
Tsai, B. S. & Lefkowitz, R. J. Molec. Pharmac. 16, 61–68 (1979).
Glossman, H. & Presek, P. Naunyn-Schmiedebergs Archs Pharmak. 306, 67–73 (1979).
Greenberg, D. A., U'Prichard, D. C., Sheehan, P. & Snyder, S. H. Brain Res. 140, 378–384 (1978).
Steer, M. L. & Wood, A. J. biol. Chem. 254, 10791–10797 (1979).
Blume, A. J., Lichtenstein, D. & Boone, G. Proc. natn. Acad. Sci. U.S.A. 76, 5626–5630 (1979).
Lichtenstein, D., Boone, G. & Blume, A. J. Cyclic Nucleotide Res. 5, 367–375 (1979).
Aktories, K., Schultz, G. & Jakobs, K. H. FEBS Lett. 107, 100–104 (1979).
Limbird, L. E., Gill, D. M. & Lefkowitz, R. J. Proc. natn. Acad. Sci. U.S.A. 77, 775–779 (1980).
Stadel, J. M., De Lean, A. & Lefkowitz, R. J. J. biol. Chem. 255, 1436–1441 (1980).
Feldman, H. A. Analyt. Biochem. 48, 317–338 (1972).
Fletcher, J. E. & Schrager, R. I. A User's Guide to Least Squares Curve Fitting Tech. Rep. No. 1 (U.S. Dep. of Health, Education and Welfare, 1973).
Rodbard, D. & Frazier, G. R. Meth. Enzym. 37B, 3–22 (1975).
De Lean, A., Munson, P. J. & Rodbard, D. Am. J. Physiol. 235, E97–E102 (1978).
Hancock, A. A., De Lean, A. & Lefkowitz, R. J. Molec. Pharmac. 16, 1–9 (1979).
Lowry, O. H., Rosebrough, N. J., Fain, A. L. & Randall, R. J. J. biol. Chem. 193, 265–275 (1951).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Michel, T., Hoffman, B. & Lefkowitz, R. Differential regulation of the α2-adrenergic receptor by Na+ and guanine nucleotides. Nature 288, 709–711 (1980). https://doi.org/10.1038/288709a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/288709a0
This article is cited by
-
Agonist high- and low-affinity states of dopamine D2 receptors: methods of detection and clinical implications
Naunyn-Schmiedeberg's Archives of Pharmacology (2013)
-
Evidence for the existence of two forms of α2A-adrenoceptors in the rat
Naunyn-Schmiedeberg's Archives of Pharmacology (1993)
-
Age-related behavioural, neurochemical and radioligand binding changes in the central 5-HT system of Sprague-Dawley rats
Psychopharmacology (1993)
-
Guanine nucleotides and pertussis toxin reduce the affinity of histamine H3 receptors on AtT-20 cells
Agents and Actions (1993)
-
Alterations in platelet alpha2-adrenoceptors by aspirin
Agents and Actions (1988)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.