Interaction of sarcolysine with. beta. -adrenergic receptors of tumor cells
The sites of specific binding of (L-/sup 3/H)dihydroalprenolol ((/sup 3/H)DHA), possessing the properties of ..beta..-adrenergic receptors, coupled with adenylate cyclase, were detected by methods of competitive displacement and binding of ..beta..-adrenoblockers: (/sup 3/H)-DHA and L-propranolol on the surface of ascites sarcoma 37 cells. Specific binding of the ligand occurs rapidly and with saturation. The total number of binding sites in the case of total saturation is (30-40) x 10/sup 3/ per cell. An analysis of the results by the Scatchard method permitted the detection of two types of ..beta..-adrenoreceptors with high (K/sub d/ = 0.9-1.0 mM) and low (K/sub d/ = 15-20 nM) affinity for (/sup 3/H)DHA. The number of receptors of the first type is (5.0-7.5) x 10/sup 3/, and of the second (20-30) x 10/sup 3/ per cell. Sarcolysine in 1-10 ..mu..M concentrations is capable of displacing (/sup 3/H)DHA bound to the ..beta..-adrenoreceptors, competing with it for common binding sites, and, like isoproterenol, inducing a brief increase in the content of cAMP in the tumor cells. Since sarcolysine noncompetitively inhibits cAMP phosphodiesterase of the plasma membranes of ascites sarcoma 37 cells in the same concentration range (2.5-25 ..mu..M), a possible functional association between the ..beta..-adrenoreceptors, adenylate cyclase, and the membrane cAMP phosphodiesterase and the participation of this complex in the antitumor effect of the cytostatic are suggested.
- Research Organization:
- All-Union Oncologic Science Center, Moscow, USSR
- OSTI ID:
- 5722078
- Journal Information:
- Biochemistry (Engl. Transl.); (United States), Vol. 50:11; Other Information: Translated from Biokhimiya; 50: No. 11, 1909-1919(Nov 1985)
- Country of Publication:
- United States
- Language:
- English
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