DIHYDROERGOCRYPTINE is a potent antagonist of α-adrenoreceptors1 that has recently been labelled to high specific radioactivity with tritium2. 3H-DHEC was found to bind to a crude membrane preparation of rabbit uterus, and a portion of this binding was suppressible by phentolamine2. The saturability, reversibility and structural and steric selectivity of this specific binding component suggested that it represents α-adrenoreceptors mediating uterine contractions2–4. In subsequent studies, 3H-DHEC was used to tentatively identify α-adrenoreceptors mediating various biological responses in several tissues5–10. The evidence for the identity of 3H-DHEC binding sites in tissue fragments with functional α-receptors in intact tissues is indirect, and is based on the demonstration of similar potencies of various ligands in suppressing 3H-DHEC binding and producing or inhibiting physiological responses. The absolute potency of particular ligands to suppress binding or affect the physiological response, often differs markedly. However, this could be due to changes in the properties of receptors caused by tissue disruption, or the different conditions in which potencies are determined. Therefore, the validity of the use of 3H-DHEC or other reversible ligands to label functionally relevant receptors must be tested in experiments where the above complications can be reduced or eliminated. We report here the use of an irreversible α-adrenoreceptor antagonist which provided a way to bridge the gap between physiological experiments measuring mechanical responses of an intact tissue and binding assays using membrane fragments, α-Receptors mediating contractions of isolated rabbit uterine strips were irreversibly blocked by phenoxybenzamine (POB), and 3H-DHEC binding was then measured in membranes prepared from these POB-treated and from untreated control strips. The results obtained dissociate phentolamine-suppressible 3H-DHEC binding and α-receptors mediating uterine contraction, but indicate that a fraction of the binding with low capacity and high affinity for DHEC, may represent true postsynaptic α-receptors.
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Rothlin, E. Bull. schweiz. Akad. med. Wiss. 2, 249–273 (1947).
Williams, L. T. & Lefkowitz, R. J. Science 192, 791–793 (1976).
Williams, L. T., Mullikin, D. & Lefkowitz, R. J. J. biol. Chem. 251, 6915–6923 (1976).
Williams, L. T. & Lefkowitz, R. J. Molec. Pharmac. 13, 304–313 (1977).
Tsai, B. S. & Lefkowitz, R. J. J. Pharmac. exp. Ther. 204, 606–614 (1978).
Strittmatter, W. J., Davis, J. N. & Lefkowitz, R. J. J. biol. Chem. 252, 5472–5477 (1977).
Guallaen, G., Yates-Aggerbeck, M., Vauquelin, G., Strosberg, D. & Hanoune, J. J. biol. Chem, 253, 1114–1120 (1978).
Kafka, M. S., Tallman, J. R., Smith, C. C. & Costa, J. L. Life Sci. 21, 1429–1438 (1977).
Greenberg, D. A., U'Prichard, D. C., Sheehan, P. & Snyder, S. H. Brain Res., 140, 378–384 (1978).
Sharma, V. K. & Banerjee, S. P. J. biol. Chem. 253, 5277–5279 (1978).
Lewis, J. E. & Miller, J. W. J. Pharmac. exp. Ther. 154, 46–55 (1966).
Dubocovich, M. & Langer, S. Z. J. Physiol., Lond. 237, 505–519 (1974).
Kalsner, S. & Nickerson, M. Br. J. Pharmac. 35, 428–439 (1969).
Yong, M. S. & Nickerson, M. J. Pharmacl. exp. Ther. 186, 100–108 (1973).
Roberts, J. M., Insel, P. A., Goldfien, R. D. & Goldfien, A. Nature 270, 624–625 (1977).
About this article
Cite this article
KUNOS, G., HOFFMAN, B., KWOK, Y. et al. Dihydroergocryptine binding and α-adrenoreceptors in smooth muscle. Nature 278, 254–256 (1979). https://doi.org/10.1038/278254a0
Fundamental & Clinical Pharmacology (1988)
European Journal of Pharmacology (1985)
Age-associated increments in human platelet α-adrenoceptor capacity. Possible mechanism for platelet hyperactivity to epinephrine in aging man
Thrombosis Research (1984)
Distribution of adrenergic receptors does not explain regional differences in blood flow in the pregnant rabbit uterus
American Journal of Obstetrics and Gynecology (1984)
Identification and characterization of α1-adrenergic receptors in human myometrium by [3H]prazosin binding
Biochemical Pharmacology (1983)