[Interaction of sarcolysine with beta-adrenoreceptors in tumor cells].

Abstract

The sites of specific binding of 3H-L-dihydroalprenolol (3H-DHA) were identified on the surface of ascites sarcoma 37 cells, using competitive displacement and binding of the beta-adrenergic antagonists, 3H-DHA and L-propranolol. These binding sites possessed the properties of beta-adrenergic receptors coupled with adenylate cyclase. Analysis of 3H-DHA binding by the Scatchard method revealed the presence of beta-adrenergic receptors of two types, i. e., with a high (Kd = 0.9-1.0 nM) and low (Kd = 15-20 nM) affinity for 3H-DHA. The number of high affinity receptors was (5.0-7.5) X 10(3); that of low affinity receptors was (20-30) X 10(3) on a per cell basis. Sarcolysine at concentrations of 1-10 microM displaced receptor-bound 3H-DHA, competed with the ligand for the common binding sites and caused, similar to isoproterenol, a short-term elevation of the intracellular cAMP content. Sarcolysine within the same concentration range (2.5-25 microM) caused non-competitive inhibition of the cAMP phosphodiesterase (PDE2) activity of plasma membranes isolated from ascites sarcoma 37 cells. The data obtained point to the functional coupling between beta-adrenergic receptors, adenylate cyclase and membraneous PDE2 of tumour cells as well as to its possible role in the antitumour effect of sarcolysine.

• Authors: A K Belousova, T I Solntseva, S V Khabarov
• Journal: Biokhimiia (Moscow, Russia) (Biokhimiia) Vol. 50 Issue 11 Pg. 1909-19 (Nov 1985) ISSN: 0320-9725 [Print] Russia (Federation)
• Vernacular Title: O vzaimodeĭstvii sarkolizina s beta-adrenoretseptorami opukholevykh kletok.
• PMID: 2998489 (Publication Type: English Abstract, Journal Article)

Chemical References

• Receptors, Adrenergic, beta
• Dihydroalprenolol
• Propranolol
• Adenylyl Cyclases
• Melphalan

Topics

• Adenylyl Cyclases (metabolism)
• Animals
• Binding Sites
• Binding, Competitive
• Dihydroalprenolol (metabolism)
• In Vitro Techniques
• Kinetics
• Melphalan (metabolism, pharmacology)
• Mice
• Models, Biological
• Propranolol (metabolism)
• Receptors, Adrenergic, beta (drug effects, metabolism)
• Sarcoma 37 (metabolism)
• Sarcoma, Experimental (metabolism)