1. Peripheral administration of a κ-opioid receptor agonist nalfurafine inactivates gonadotropin-releasing hormone pulse generator activity in goats.
- Author
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Matsuda F, Ito D, Wakabayashi Y, Yamamura T, Okamura H, and Ohkura S
- Subjects
- Animals, Female, Luteinizing Hormone blood, Luteinizing Hormone metabolism, Kisspeptins metabolism, Dynorphins metabolism, Neurons drug effects, Neurons metabolism, Neurokinin B metabolism, Goats, Receptors, Opioid, kappa agonists, Receptors, Opioid, kappa metabolism, Spiro Compounds pharmacology, Spiro Compounds administration & dosage, Gonadotropin-Releasing Hormone metabolism, Gonadotropin-Releasing Hormone agonists, Morphinans pharmacology, Arcuate Nucleus of Hypothalamus drug effects, Arcuate Nucleus of Hypothalamus metabolism
- Abstract
Neurons co-expressing kisspeptin, neurokinin B, and dynorphin A (KNDy neurons), located in the arcuate nucleus (ARC) of the hypothalamus, are indicated to be the gonadotropin-releasing hormone (GnRH) pulse generator. Dynorphin A is reported to suppress GnRH pulse generator activity. Nalfurafine is a selective agonist of the κ-opioid receptor (KOR), a receptor for dynorphin A, clinically used as an anti-pruritic drug. This study aimed to evaluate the effects of nalfurafine on GnRH pulse generator activity and luteinizing hormone (LH) pulses using female goats. Nalfurafine (0, 2, 4, 8, or 16 μg/head) was intravenously injected into ovariectomized Shiba goats. The multiple unit activity (MUA) in the ARC area was recorded, and plasma LH concentrations were measured 2 and 48 h before and after injection, respectively. The MUA volley interval during 0-2 h after injection was significantly increased in the nalfurafine 8 and 16 μg groups compared with the vehicle group. In 0-2 h after injection, the number of LH pulses was significantly decreased in the nalfurafine 8 and 16 μg groups, and the mean and baseline LH were significantly decreased in all nalfurafine-treated groups (2, 4, 8, and 16 μg) compared with the vehicle group. These results suggest that nalfurafine inhibits the activity of the GnRH pulse generator in the ARC, thus suppressing pulsatile LH secretion. Therefore, nalfurafine could be used as a reproductive inhibitor in mammals., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This study was partly supported by funds donated by Toray Industries, Inc., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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