Endomorphin-1 and endomorphin-2, endogenous ligands for the μ-opioid receptor, inhibit electrical activity of rat rostral ventrolateral medulla neurons in vitro
Section snippets
Animals
Male Sprague–Dawley rats weighing 100–150 g (Animal Facility of Shanghai Medical University, PRC) were used in this study. Before use, rats were housed three or four to a clear plastic cage and maintained on a 12-h/12-h light/dark schedule, with food and water provided ad libitum. All animal use procedures were in strict accordance with the NIH Guide for the Care and Use of Laboratory Animals.
Single-unit recording in brain slices
Recording of single-unit discharge in rat brain slices containing the RVLM was conducted according to
Effects of endomorphin-1 and endomorphin-2 perfusion on firing rate of rostral ventrolateral medulla neurons
In this study, we recorded a total of 78 units with spontaneous firing activity in the RVLM region. The spontaneous activity was either regular or irregular, with a range of 2–26 Hz (mean±S.E.M.: 8.3±1.6 Hz). Among these neurons, we then tested the effects of EM-1 and EM-2 perfusion on neuronal firing rate in 65 and 42 units, respectively. Following EM-1 perfusion at a concentration of 10 nM, spontaneous discharges of 43% (28 of 65) of neurons were nearly abolished (see a representative recording
Discussion
Single-unit recording from rat brain slices was utilized to explore the effects of EM-1 and EM-2 on the electrical activity of the CNS neurons. We found that EM-1 and EM-2 perfusion considerably inhibited the spontaneous firing frequency of 43% and 38% of neurons recorded from the RVLM region, respectively. Both endomorphins produced this suppression in a concentration-dependent manner. However, EM-1 was approximately threefold more potent than EM-2 in depressing RVLM neuronal firing. The
Conclusion
The effects of EM-1 and EM-2, the recently isolated endogenous ligands for the μ-opioid receptor, on the electrical activity of neurons recorded from the RVLM in rat brain slices were investigated in this study. Like other opioid peptides (met-ENK and nociceptin), both EM-1 and EM-2 concentration-dependently inhibited the spontaneous discharges of RVLM neurons. In this action, EM-1 was more potent than EM-2, as EM-1-induced suppression was greater and longer than that induced by EM-2 at all
Acknowledgements
This work was supported, in part, by grants 39570272 (to P.L.) from the National Nature Science Foundation of China and the National Key Lab of Medical Neurobiology of China, and 9960266Z (to J.Q.W.) from the American Heart Association. We wish to thank Dr Y. X. Cao for technical assistance.
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