TY - JOUR
T1 - Electrophysiological and behavioral effects of Tyr-D-Arg-Phe-Sar on locus coeruleus neurons of the rat
AU - Yang, Yea Ru
AU - Lee, Eminy H.Y.
AU - Chiu, Tsai Hsien
N1 - Funding Information:
This work was supported in part by NSC 84-2331-B-010-111 (to T.H.C.) from the National Science Council. We appreciate Mr. Al Vendouris for his editing and English language consultancy.
PY - 1998/6/12
Y1 - 1998/6/12
N2 - The effect of Tyr-D-Arg-Phe-Sar (TAPS), a μ-selective tetrapeptide analog of dermorphin, was studied in the rat both in vitro, using slices of the locus coeruleus, and in vivo, after microinjection into the locus coeruleus. In electrophysiological studies, TAPS (1-100 nM) was able to inhibit spontaneous firing, cause hyperpolarization of the membrane potential and reduce the input resistance of neurons of the locus coeruleus, suggesting that there was an effect on the potassium channels. Based on the inhibition of the spontaneous firing rate, the average IC50 for TAPS was calculated to be 1.9 nM, a value lower than that reported for dermorphin or morphine. The TAPS-induced effects were antagonized by naloxone, with a dissociation equilibrium constant of 1.96 ± 0.14 nM. The results indicate that TAPS binds to μ-opioid receptors on the cell membrane of neurons of the locus coeruleus to cause its inhibitory actions. In behavioral study, TAPS was microinjected bilaterally via chronically implanted cannulae into the locus coeruleus of non-anesthetized rats and its effects on locomotor activity determined. TAPS, at concentrations of 1 μM and 10 μM, but not of 0.1 μM, induced hypolocomotion/sedation and the effect was significantly reversed by naloxone (5 mg/kg i.p.). Taken together, these data suggest that TAPS has an inhibitory effect on neurons of the locus coeruleus and produces hypolocomotive/sedative effects in vivo.
AB - The effect of Tyr-D-Arg-Phe-Sar (TAPS), a μ-selective tetrapeptide analog of dermorphin, was studied in the rat both in vitro, using slices of the locus coeruleus, and in vivo, after microinjection into the locus coeruleus. In electrophysiological studies, TAPS (1-100 nM) was able to inhibit spontaneous firing, cause hyperpolarization of the membrane potential and reduce the input resistance of neurons of the locus coeruleus, suggesting that there was an effect on the potassium channels. Based on the inhibition of the spontaneous firing rate, the average IC50 for TAPS was calculated to be 1.9 nM, a value lower than that reported for dermorphin or morphine. The TAPS-induced effects were antagonized by naloxone, with a dissociation equilibrium constant of 1.96 ± 0.14 nM. The results indicate that TAPS binds to μ-opioid receptors on the cell membrane of neurons of the locus coeruleus to cause its inhibitory actions. In behavioral study, TAPS was microinjected bilaterally via chronically implanted cannulae into the locus coeruleus of non-anesthetized rats and its effects on locomotor activity determined. TAPS, at concentrations of 1 μM and 10 μM, but not of 0.1 μM, induced hypolocomotion/sedation and the effect was significantly reversed by naloxone (5 mg/kg i.p.). Taken together, these data suggest that TAPS has an inhibitory effect on neurons of the locus coeruleus and produces hypolocomotive/sedative effects in vivo.
KW - Intracellular recording
KW - Locomotor activity
KW - Locus coeruleus
KW - Tyr-D-Arg-Phe-Sar
UR - http://www.scopus.com/inward/record.url?scp=0032511172&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(98)00296-9
DO - 10.1016/S0014-2999(98)00296-9
M3 - Article
C2 - 9698201
AN - SCOPUS:0032511172
SN - 0014-2999
VL - 351
SP - 23
EP - 30
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -