N-Methyl-d-aspartic Acid (NMDA) Receptor Is Involved in the Inhibitory Effect of Ketamine on Human Sperm Functions

Ying Chen,Yuan Yuan,Shuangyan Zheng,Wenqing Xu,Tao Luo,Houyang Chen,Yuanqiao He

doi:10.3390/ijms222212370

Ying Chen, Yuan Yuan + Show 5 more

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https://doi.org/10.3390/ijms222212370

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Abstract

Ketamine, which used to be widely applied in human and animal medicine as a dissociative anesthetic, has become a popular recreational drug because of its hallucinogenic effect. Our previous study preliminarily proved that ketamine could inhibit human sperm function by affecting intracellular calcium concentration ([Ca2+]i). However, the specific signaling pathway of [Ca2+]i induced by ketamine in human sperm is still not clear yet. Here, the N-methyl-d-aspartic acid (NMDA) receptor was detected in the tail region of human sperm. Its physiological ligand, NMDA (50 μM), could reverse ketamine’s inhibitory effect on human sperm function, and its antagonist, MK801 (100 μM), could restrain the effect of NMDA. The inhibitory effect caused by 4 mM ketamine or 100 μM MK801 on [Ca2+]i, which is a central factor in the regulation of human sperm function, could also be recovered by 50 μM NMDA. The results suggest that the NMDA receptor is probably involved in the inhibitory effect of ketamine on human sperm functions.

Highlights

Ketamine used to be widely applied in human and veterinary medicine as a dissociative anesthetic
Considering that the NMDA receptor is the main target of ketamine, studying these issues will contribute to further elucidating the mechanism of ketamine in the function of mature human sperm
The results showed that 4 mM ketamine could remarkably reduce the capacitation and acrosome reaction rate, both of which could be significantly recovered by 50 μM NMDA (Figure 3E,F)

Summary

Introduction

Ketamine used to be widely applied in human and veterinary medicine as a dissociative anesthetic. A previous study preliminarily demonstrated that ketamine could inhibit human sperm function by reducing intracellular calcium concentration ([Ca2+]i) [2]. It can block NMDA receptors to impact the normal physiological function of cells, especially in neurons [3]. It has been reported that ketamine inhibits the NMDA receptor by two distinct mechanisms. It either blocks the open channel by reducing the mean channel open time or decreases the frequency of opening for the closed channel by an allosteric mechanism [4]. The NMDA receptor is a ligand-gated cation channel that causes Ca2+ influx in neurons, it has functions in the reproductive system of various species

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