Moon C, Jaberi P, Otto-Bruc A, Baehr W, Palczewski K, Ronnett G V
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Neurosci. 1998 May 1;18(9):3195-205. doi: 10.1523/JNEUROSCI.18-09-03195.1998.
The second messengers cAMP and inositol-1,4,5-triphosphate have been implicated in olfaction in various species. The odorant-induced cGMP response was investigated using cilia preparations and olfactory primary cultures. Odorants cause a delayed and sustained elevation of cGMP. A component of this cGMP response is attributable to the activation of one of two kinetically distinct cilial receptor guanylyl cyclases by calcium and a guanylyl cyclase-activating protein (GCAP). cGMP thus formed serves to augment the cAMP signal in a cGMP-dependent protein kinase (PKG) manner by direct activation of adenylate cyclase. cAMP, in turn, activates cAMP-dependent protein kinase (PKA) to negatively regulate guanylyl cyclase, limiting the cGMP signal. These data demonstrate the existence of a regulatory loop in which cGMP can augment a cAMP signal, and in turn cAMP negatively regulates cGMP production via PKA. Thus, a small, localized, odorant-induced cAMP response may be amplified to modulate downstream transduction enzymes or transcriptional events.
第二信使环磷酸腺苷（cAMP）和肌醇-1,4,5-三磷酸已被证实参与多种物种的嗅觉过程。本研究利用纤毛制剂和嗅觉原代培养物对气味剂诱导的环磷酸鸟苷（cGMP）反应进行了探究。气味剂可导致cGMP出现延迟且持续的升高。这种cGMP反应的一部分归因于两种动力学特性不同的纤毛受体鸟苷酸环化酶之一被钙和一种鸟苷酸环化酶激活蛋白（GCAP）激活。如此形成的cGMP通过直接激活腺苷酸环化酶，以依赖cGMP的蛋白激酶（PKG）方式增强cAMP信号。反过来，cAMP激活依赖cAMP的蛋白激酶（PKA）以负向调节鸟苷酸环化酶，从而限制cGMP信号。这些数据证明存在一种调节环路，其中cGMP可增强cAMP信号，而cAMP又通过PKA负向调节cGMP的产生。因此，由气味剂诱导产生的小范围、局部性的cAMP反应可能会被放大，从而调节下游的转导酶或转录事件。
