Molecular Pharmacology, Vol 20, 463-469, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Presence of Both Beta₁- and Beta₂-Adrenergic Receptors in a Single Cell Type

¹ Laboratoire de Physiologie Cellulaire et Laboratoire de Neuroendocrinologie Cellulaire, Collège de France, 75231 Paris Cedex 05, France

Many tissues, including lung, heart, and brain, have been shown to contain beta₁ and beta₂-adrenergic receptor subtypes. This raises the question of whether receptor subtype heterogeneity corresponds to cell type heterogeneity within the tissue, or whether beta₁- and beta₂-receptors can coexist in the same cell. We have shown, by both radioligand binding studies and adenylate cyclase experiments, that these two receptor subtypes coexist in C₆ cloned glioma cells and in three derived subclones. Competition experiments in binding and adenylate cyclase assays were conducted using membranes of C₆ glioma cells and of three derived subclones. When [³H]dihydroalprenolol was used as the radioactive ligand, graphic and computer analysis of the competition binding curves obtained with beta₁- or beta₂-specific drugs always indicated a heterogeneity of beta-adrenergic receptors. For C₆ glioma cell membranes, computer analysis indicated the presence of 80-90% beta₁-receptors and 10-20% beta₂-receptors. The same results were obtained with the three subclones. Analysis of the curves for the inhibition of isoproterenol-stimulated adenylate cyclase by practolol, a beta₁-selective antagonist, showed the presence of two components. The heterogeneity of these practolol inhibition curves indicated that both types of beta-adrenergic receptors are coupled to the cyclase. Analysis of the dose-response curves of adenylate cyclase activation obtained with specific beta₂-agonists also showed a heterogeneity of the response. This finding suggested that occupation of the beta₂-receptors by a beta₂-agonist was responsible for most of the cyclase activation and also that occupation of beta₁-receptors by such an agonist can lead to stimulation of the enzyme but with a less efficient coupling. In conclusion, both beta₁- and beta₂-adrenergic receptors coupled to adenylate cyclase can coexist on a single cell.

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ACKNOWLEDGMENTS We are indebted to Miss Dreyfus and Mrs. du Parc for preparation of the manuscript.

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