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Molecular Pharmacology

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Abstract

Direct effects of thymopentin (Arg-Lys-Asp-Val-Tyr) on cholinergic agonist-induced slow inactivation of nicotinic acetylcholine receptor function.

E L Ochoa, L A Li, A Plummer and M G McNamee
Molecular Pharmacology December 1990, 38 (6) 863-871;
E L Ochoa
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L A Li
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A Plummer
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M G McNamee
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Abstract

The effects of thymopentin (TP-5) on the cholinergic agonist-induced inactivation of function (desensitization) of the nicotinic acetylcholine receptor (nAChR) were explored using two systems, 1) Torpedo californica electroplax nAchR reconstituted into phospholipid vesicles and 2) T. californica nAChR expressed, in Xenopus laevis oocytes, from in vitro synthesized RNA transcripts. The pentapeptide did not modify the equilibrium binding of 125I-alpha-bungarotoxin, but toxin rate binding assays in the presence of the cholinergic agonist carbamylcholine (Carb) revealed that it shortened the time course of the Carb-induced nAchR transition to the high affinity, desensitized state. Thymopentin (but not thymosins alpha 1 and beta 4) accelerated the slow inactivation of nAchR-mediated 86Rb+ influx, as measured by the first-order decrease in the Carb-induced 86Rb+ transport into the reconstituted vesicles. The decay of the acetylcholine-induced current from Torpedo receptor expressed in oocytes was also accelerated by TP-5. The pentapeptide had no ion channel-blocking or agonist activity of its own and exhibited a requirement for Ca2+ to express its effects. On the basis of these results, it is proposed that TP-5 has a direct effect on the nAChR, resembling that of noncompetitive blockers, as opposed to an indirect mechanism of action via the activation of specific metabolic pathways.

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Molecular Pharmacology
Vol. 38, Issue 6
1 Dec 1990
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Abstract

Direct effects of thymopentin (Arg-Lys-Asp-Val-Tyr) on cholinergic agonist-induced slow inactivation of nicotinic acetylcholine receptor function.

E L Ochoa, L A Li, A Plummer and M G McNamee
Molecular Pharmacology December 1, 1990, 38 (6) 863-871;

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Abstract

Direct effects of thymopentin (Arg-Lys-Asp-Val-Tyr) on cholinergic agonist-induced slow inactivation of nicotinic acetylcholine receptor function.

E L Ochoa, L A Li, A Plummer and M G McNamee
Molecular Pharmacology December 1, 1990, 38 (6) 863-871;
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