Tramadol-induced block of hyperpolarization-activated cation current in rat pituitary lactotrophs

Yen Chin Liu, Ya Jean Wang, Pei Yu Wu, Sheng Nan Wu

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)127-135
Number of pages9
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume379
Issue number2
DOIs
Publication statusPublished - 2009 Feb

All Science Journal Classification (ASJC) codes

  • Pharmacology

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