Adrenergic and antiadrenergic activity of cycloheximide in cultured rat heart cells.

Cycloheximide at concentrations between 10(-5) to 10(-3) M increased the rate of beating of rocker-cultured neonatal rat myocardial cells through activation of alpha 1-adrenoceptors. At concentrations between 3 X 10(-10) and 10(-6) M, at which [14C]-leucine incorporation into the cultured cells was not or not greatly affected, the antibiotic inhibited surmountably the positive chronotropic action of the rather nonselective beta-adrenergic agonist isoprenaline. It also antagonized the cyclic AMP response to isoprenaline. A powerful positive chronotropic action of the beta 2-selective agonist clenbuterol was not opposed by cycloheximide. Neither did cycloheximide (10(-8) and 10(-6) M) influence the acceleration of beating by phenylephrine, dibutyryl cyclic AMP, and elevation of the extracellular calcium concentration. Displacement of the nonselective beta-adrenoceptor ligand [125I]iodopindolol from its specific binding sites on the cultured heart cells by cycloheximide was diphasic, with 15 to 35 per cent of the displacement taking place below 10(-8) M cycloheximide (IC50 = = 2 X 10(-9) M) and the remaining 65 to 85 per cent above 10(-5) M. The action of low concentrations of cycloheximide on beta-adrenoceptors remains to be delineated.