[Interaction of sarcolysine with beta-adrenoreceptors in tumor cells].
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.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D004082:Dihydroalprenolol / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008558:Melphalan / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D011433:Propranolol / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012511:Sarcoma 37 / Q000378:metabolism*; D012513:Sarcoma, Experimental / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D011433:Propranolol; D000262:Adenylyl Cyclases; D008558:Melphalan
O vzaimodeĭstvii sarkolizina s beta-adrenoretseptorami opukholevykh kletok.