Wollenberger A, Wallukat G
Biomed Biochim Acta. 1983;42(7-8):917-29.
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.
浓度在10⁻⁵至10⁻³M之间的放线菌酮通过激活α1 -肾上腺素能受体增加了摇床培养的新生大鼠心肌细胞的搏动速率。在3×10⁻¹⁰至10⁻⁶M的浓度范围内，[¹⁴C] -亮氨酸掺入培养细胞的过程未受或未受显著影响，该抗生素可克服性地抑制相当非选择性的β -肾上腺素能激动剂异丙肾上腺素的正性变时作用。它还拮抗了对异丙肾上腺素的环磷酸腺苷反应。β2 -选择性激动剂克仑特罗的强大正性变时作用不受放线菌酮的对抗。放线菌酮（10⁻⁸和10⁻⁶M）也不影响去氧肾上腺素、二丁酰环磷酸腺苷以及细胞外钙浓度升高所引起的搏动加速。放线菌酮使非选择性β -肾上腺素能受体配体[¹²⁵I]碘吲哚洛尔从培养的心脏细胞上的特异性结合位点发生位移呈双相性，在放线菌酮浓度低于10⁻⁸M时发生15%至35%的位移（半数抑制浓度=2×10⁻⁹M），其余65%至85%的位移发生在10⁻⁵M以上。低浓度放线菌酮对β -肾上腺素能受体的作用仍有待阐明。
