Li Y, Goldbeter A
Faculté des Sciences, Université Libre de Bruxelles, Belgium.
Biophys J. 1989 Jan;55(1):125-45. doi: 10.1016/S0006-3495(89)82785-7.
Cells often communicate by means of periodic signals, as exemplified by a large number of hormones and by the aggregation of Dictyostelium discoideum amebas in response to periodic pulses of cyclic AMP. Periodic signaling allows bypassing the phenomenon of desensitization brought about by constant stimuli. To gain further insight into the efficiency of pulsatile signaling, we analyze the effect of periodic stimulation on the dynamic behavior of a receptor system capable of desensitization toward its ligand. We first show that the receptor system adapts to square-wave stimuli, i.e., the response eventually reaches a steady, periodic pattern after a transient phase. By analyzing the dependence of the response on the characteristics of the square-wave stimulation, we show that there exist a waveform and a period of that signal that result in maximum responsiveness of the target system. Similar results are obtained when the signal takes the more realistic form of a periodically repeated stimulation followed by exponential decay of the ligand. The results are discussed with respect to the role of pulsatile secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus and of periodic signaling by cyclic AMP pulses in Dictyostelium. The analysis accounts for the existence, in both cases, of an optimal frequency and waveform of the periodic stimulus that correspond to maximum target cell responsiveness.
细胞常常通过周期性信号进行通讯，大量激素以及盘基网柄菌变形虫对周期性环磷酸腺苷脉冲作出反应而聚集就是例证。周期性信号传导能够避开持续刺激所引发的脱敏现象。为了进一步深入了解脉动信号传导的效率，我们分析了周期性刺激对一个能够对其配体产生脱敏作用的受体系统动态行为的影响。我们首先表明，该受体系统能适应方波刺激，也就是说，在经过一个瞬态阶段后，反应最终会达到一种稳定的周期性模式。通过分析反应对方波刺激特征的依赖性，我们发现存在一种波形以及该信号的一个周期，它们会导致靶系统的反应性达到最大值。当信号采用更符合实际的形式，即周期性重复刺激后接着配体呈指数衰减时，也能得到类似结果。我们结合下丘脑促性腺激素释放激素（GnRH）的脉动分泌以及盘基网柄菌中由环磷酸腺苷脉冲进行的周期性信号传导的作用来讨论这些结果。该分析解释了在这两种情况下都存在与最大靶细胞反应性相对应的周期性刺激的最佳频率和波形。
