TY - JOUR
T1 - Tramadol-induced block of hyperpolarization-activated cation current in rat pituitary lactotrophs
AU - Liu, Yen Chin
AU - Wang, Ya Jean
AU - Wu, Pei Yu
AU - Wu, Sheng Nan
N1 - Funding Information:
Acknowledgements This work was partly supported by National Science Council (NSC-92–2320-B-075B-001, NSC-95-2314-B-006-092), Taiwan.
PY - 2009/2
Y1 - 2009/2
N2 - The hyperpolarization-activated cation current (I h) in rat pituitary lactotrophs (GH3 cells) was characterized. Tramadol-induced block of this current was investigated. Effects of various related compounds on I h in GH3 cells were also compared. Tramadol caused a time- and concentration-dependent reduction in the amplitude of I h with an IC50 value of 13.6 μM. ZD7288 (30 μM), CsCl (2 mM), and propofol (30 μM) were effective in suppressing the amplitude of I h. 2,5-dideoxyadenosine (100 μM) suppressed I h, while sp-cAMPS (100 μM) had no effect on it. Tramadol (10 μM) 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 μM) could reduce the firing frequency of action potentials. Intracellular Ca2+ measurements revealed its ability to reduce spontaneous Ca2+ oscillations in GH3 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.
AB - The hyperpolarization-activated cation current (I h) in rat pituitary lactotrophs (GH3 cells) was characterized. Tramadol-induced block of this current was investigated. Effects of various related compounds on I h in GH3 cells were also compared. Tramadol caused a time- and concentration-dependent reduction in the amplitude of I h with an IC50 value of 13.6 μM. ZD7288 (30 μM), CsCl (2 mM), and propofol (30 μM) were effective in suppressing the amplitude of I h. 2,5-dideoxyadenosine (100 μM) suppressed I h, while sp-cAMPS (100 μM) had no effect on it. Tramadol (10 μM) 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 μM) could reduce the firing frequency of action potentials. Intracellular Ca2+ measurements revealed its ability to reduce spontaneous Ca2+ oscillations in GH3 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.
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U2 - 10.1007/s00210-008-0353-0
DO - 10.1007/s00210-008-0353-0
M3 - Article
C2 - 18818902
AN - SCOPUS:64949172201
SN - 0028-1298
VL - 379
SP - 127
EP - 135
JO - Naunyn-Schmiedeberg's Archives of Pharmacology
JF - Naunyn-Schmiedeberg's Archives of Pharmacology
IS - 2
ER -