title: Ca2+ transient evoked by chemical stimulation is enhanced by PGE2 in vagal sensory neurons: role of cAMP/PKA signaling pathway.
abstract: The effect of prostaglandin E(2) (PGE(2)) on chemical stimulation-evoked calcium (Ca(2+)) transient was investigated in isolated vagal sensory neurons of the rat using fura-2-based ratiometric Ca(2+) imaging. Application of capsaicin (3 x 10(-8) to 10(-7) M; 15 s) caused a rapid surge of intracellular Ca(2+) concentration in small- and medium-size neurons; the response was reproducible when >10 min elapsed between two challenges and was absent in nominally Ca(2+)-free solution. After pretreatment with PGE(2) (3 x 10(-7) M; 5 min), the peak of this capsaicin-evoked Ca(2+) transient was increased by almost fourfold, and its duration was also prolonged. This augmented response to capsaicin induced by PGE(2) gradually declined but remained higher than control after 15-min washout. Similarly, PGE(2) pretreatment also markedly enhanced the Ca(2+) transients induced by other chemical stimulants to C neurons, such as phenylbiguanide (PBG), adenosine 5'-triphosphate (ATP), and KCl. The Ca(2+) transients evoked by PBG, ATP, and KCl were potentiated after the pretreatment with PGE(2) to 242, 204, and 163% of their control, respectively. This potentiating effect of PGE(2) could be mimicked by forskolin (10(-6) M; 5 min), an activator of adenylyl cyclase, and 8-(4-chlorophenylthio)adenosine-3'-5'-cyclic monophosphate (CPT-cAMP; 3 x 10(-6) M, 10 min), a membrane-permeable cAMP analogue. Furthermore, the potentiating effects of PGE(2), forskolin, and CPT-cAMP were abolished by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89; 10(-5) M; 15-20 min), a protein kinase A (PKA) inhibitor. In summary, these results show that PGE(2) reversibly potentiates the chemical stimuli-evoked Ca(2+) transients in cultured rat vagal sensory neurons, and this potentiating effect is mediated through the cyclic AMP/PKA transduction cascade.
authors.affiliation: Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA.
authors.forename: Qihai
authors.initials: Q
authors.lastname: Gu
authors.forename: Kevin
authors.initials: K
authors.lastname: Kwong
authors.forename: Lu-Yuan
authors.initials: LY
authors.lastname: Lee
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009620:Nodose Ganglion / Q000166:cytology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013268:Stimulation, Chemical; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D013873:Thionucleotides; D005576:Colforsin; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone; D002211:Capsaicin; D002118:Calcium