title: Tramadol-induced block of hyperpolarization-activated cation current in rat pituitary lactotrophs.
abstract: The hyperpolarization-activated cation current (I (h)) in rat pituitary lactotrophs (GH(3) cells) was characterized. Tramadol-induced block of this current was investigated. Effects of various related compounds on I (h) in GH(3) cells were also compared. Tramadol caused a time- and concentration-dependent reduction in the amplitude of I (h) with an IC(50) value of 13.6 microM. ZD7288 (30 microM), CsCl (2 mM), and propofol (30 microM) were effective in suppressing the amplitude of I (h). 2',5'-dideoxyadenosine (100 microM) suppressed I (h), while sp-cAMPS (100 microM) had no effect on it. Tramadol (10 microM) shifted the activation curve of I (h) to a more negative potential by approximately -20 mV, although no change in the slope factor was observed. Under current-clamp configuration, tramadol (10 microM) could reduce the firing frequency of action potentials. Intracellular Ca(2+) measurements revealed its ability to reduce spontaneous Ca(2+) oscillations in GH(3) cells. The results suggests that during cell exposure to tramadol used at clinically relevant concentration, the tramadol-mediated inhibition of I (h) could be direct and mediated via a non-opioid mechanism and would be one of the ionic mechanisms underlying reduced cell excitability.
authors.affiliation: Department of Anesthesiology, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: Yen-Chin
authors.initials: YC
authors.lastname: Liu
authors.forename: Ya-Jean
authors.initials: YJ
authors.lastname: Wang
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Wu
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Wu
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002412:Cations; D002460:Cell Line; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016048:Dideoxyadenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D052682:Lactotrophs / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D013873:Thionucleotides / Q000494:pharmacology; D014147:Tramadol / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D002412:Cations; D002712:Chlorides; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D011743:Pyrimidines; D013873:Thionucleotides; C082246:ICI D2788; D002586:Cesium; C016957:adenosine-3',5'-cyclic phosphorothioate; D014147:Tramadol; D016048:Dideoxyadenosine; C021008:2',5'-dideoxyadenosine; D000242:Cyclic AMP; C028019:cesium chloride; D015742:Propofol