Ca Transient Evoked by Chemical Stimulation Is Enhanced by PGE2 in Vagal Sensory Neurons: Role of cAMP/PKA Signaling Pathway

Gu, Qihai, Kevin Kwong, and Lu-Yuan Lee. Ca transient evoked by chemical stimulation is enhanced by PGE2 in vagal sensory neurons: role of cAMP/PKA signaling pathway. J Neurophysiol 89: 1985–1993, 2003. First published December 4, 2002; 10.1152/jn.00748.2002. The effect of prostaglandin E2 (PGE2) on chemical stimulation-evoked calcium (Ca 2 ) transient was investigated in isolated vagal sensory neurons of the rat using fura-2-based ratiometric Ca imaging. Application of capsaicin (3 10 8 to 10 7 M; 15 s) caused a rapid surge of intracellular Ca concentration in smalland medium-size neurons; the response was reproducible when 10 min elapsed between two challenges and was absent in nominally Ca -free solution. After pretreatment with PGE2 (3 10 7 M; 5 min), the peak of this capsaicin-evoked Ca transient was increased by almost fourfold, and its duration was also prolonged. This augmented response to capsaicin induced by PGE2 gradually declined but remained higher than control after 15-min washout. Similarly, PGE2 pretreatment also markedly enhanced the Ca transients induced by other chemical stimulants to C neurons, such as phenylbiguanide (PBG), adenosine 5 -triphosphate (ATP), and KCl. The Ca transients evoked by PBG, ATP, and KCl were potentiated after the pretreatment with PGE2 to 242, 204, and 163% of their control, respectively. This potentiating effect of PGE2 could be mimicked by forskolin (10 6 M; 5 min), an activator of adenylyl cyclase, and 8-(4-chlorophenylthio)adenosine3 -5 -cyclic monophosphate (CPT-cAMP; 3 10 6 M, 10 min), a membrane-permeable cAMP analogue. Furthermore, the potentiating effects of PGE2, forskolin, and CPT-cAMP were abolished by N-[2-(pbromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89; 10 5 M; 15–20 min), a protein kinase A (PKA) inhibitor. In summary, these results show that PGE2 reversibly potentiates the chemical stimulievoked Ca transients in cultured rat vagal sensory neurons, and this potentiating effect is mediated through the cyclic AMP/PKA transduction cascade.