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Sci Rep. 2016 Aug 30;6:32255. doi: 10.1038/srep32255.

Characterization of non-olfactory GPCRs in human sperm with a focus on GPR18.

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Ruhr-University Bochum, Department of Cell Physiology, Bochum, Germany.
Department of Dermatology, Venerology, and Allergology, University Hospital Essen, University of Duisburg-Essen, Germany.
Pharma-Zentrum Bonn, Pharmazeutisches Institut, Pharmazeutische Chemie, Universität Bonn, Bonn, Germany.
Jagiellonian University Medical College, Faculty of Pharmacy, Department of Technology and Biotechnology of Drugs, Medyczna 9, PL-30-688 Kraków, Poland.
Competence Network for HIV/AIDS, Ruhr University Bochum, Bochum, Germany.
Department of Dermatology, Venerology, and Allergology, Center for sexuell health, Ruhr University Bochum, Bochum, Germany.
University of Köln, Cologne Center for Genomics, Köln, Germany.


G protein-coupled receptors (GPCRs) transduce external chemical cues into intracellular signals and are involved in a plethora of physiological processes, but knowledge regarding the function of these receptors in spermatozoa is limited. In the present study, we performed RNA-Seq and analyzed the expression of the all GPCRs except olfactory receptors in human spermatozoa. We revealed the expression of up to 223 different GPCR transcripts in human spermatozoa (FPKM > 0.1) and identified GPR18, a newly described cannabinoid receptor, together with GPR137 and GPR135, as one of the three most highly expressed GPCRs. To date, the expression of GPR18 was completely unknown in human spermatozoa. We confirmed GPR18 expression using RT-PCR and immuncytochemistry experiments and localized the GPR18 protein in the midpiece of human spermatozoa. Stimulation of human spermatozoa with the GPR18 ligand N-arachidonoylglycine induced the phosphorylation of 12 protein kinases, some of them are for example known to be involved in the acrosome reaction. In line with this, N-arachidonoylglycine affected the cytoskeleton by changing levels of F-actin and inducing the acrosome reaction in human spermatozoa in a concentration-dependent manner. Our results indicate that GPR18 might be involved in physiological processes of human spermatozoa, suggesting GPR18 to be a potential player in sperm physiology.

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