Adenosine and Catecholamine Agonists Speed the Flagellar Beat of Mammalian Sperm by a Non-Receptor-Mediated Mechanism1

Schuh, Sonya M.; Hille, Bertil; Babcock, Donner F.

doi:10.1095/biolreprod.107.062562

Cited by 22 publications

(25 citation statements)

References 47 publications

(82 reference statements)

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“…Adenosine Transporters in Acceleration of the Sperm Flagellar Beat-Our past work suggested that adenosine and related analogs may enter sperm via equilibrative and concentrative nucleoside transporters (ENTs and CNTs) to engage a cAMPmediated signaling pathway that increases sperm flagellar beat frequency (10,11). For the mouse, the Slc28a1-3 genes encode CNT1-3 (25) and Slc29a1-4 genes encode ENT1-4 (26).…”

Section: Resultsmentioning

confidence: 99%

“…This approach has provided definitive evidence for required roles of the unique CatSper ion channel proteins (1)(2)(3)(4)(5)(6)(7), for the atypical sperm adenylyl cyclase SACY 2 (3,8), and for the sperm-specific C␣2 catalytic subunit of PKA (9,10). It also produced the unexpected finding that adenosine analogs engage cAMP-mediated signaling to increase flagellar beat frequency (10,11).…”

mentioning

confidence: 99%

“…However, in sperm the predominant (perhaps the only) adenylyl cyclase is the atypical SACY (ADCY10) (8), which lacks transmembrane domains and is unaffected by G-proteins (14,15). The apparent absence of conventional adenylyl cyclases led us to propose that adenosine analogs may enter sperm via cell surface nucleoside transporters to engage the SACY/PKA signaling pathway (10,11). We now reconsider this proposal, evaluating the expression of Slc28a and Slc29a nucleoside transporters in adult mouse testis, and examining the phenotype of sperm from the Slc29a1 knock-out mouse (16).…”

mentioning

confidence: 99%

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Testicular Expression of Adora3i2 in Adora3 Knockout Mice Reveals a Role of Mouse A3Ri2 and Human A3Ri3 Adenosine Receptors in Sperm*

Burnett¹,

Blais²,

Unadkat

et al. 2010

Journal of Biological Chemistry

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Adenosine is a candidate modulator of sperm motility in the female reproductive tract that increases sperm flagellar beat frequency in vitro. Past work suggested that this acceleration may involve equilibrative (ENT) and concentrative (CNT) nucleoside transporters. Here we show that Slc29a1 (ENT-1) is the predominant nucleoside transporter expressed in the mouse testis. Unexpectedly, the beat of Slc29a1-null sperm still accelerates in response to 2-chloro-2-deoxyadenosine (Cl-dAdo). The only known roles of sperm are to reach the egg and deliver its genetic payload and to initiate early signaling events in the zygote. Although the list is short, the tasks are complex, and the sperm requires numerous specialized components to accomplish these goals. Our recent work has focused on how the sperm applies its specialized components to control swimming behavior. We have combined biophysical methods with a genetic approach, using sperm from null-mutant (knock-out) mice that carry targeted disruptions of the genes for several of the components of the signaling pathways that operate in the sperm flagellum. This approach has provided definitive evidence for required roles of the unique CatSper ion channel proteins (1-7), for the atypical sperm adenylyl cyclase SACY 2

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Testicular Expression of Adora3i2 in Adora3 Knockout Mice Reveals a Role of Mouse A3Ri2 and Human A3Ri3 Adenosine Receptors in Sperm*

Burnett¹,

Blais²,

Unadkat

et al. 2010

Journal of Biological Chemistry

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“…Importantly, adenosine is a key molecule for sperm capacitation, the series of changes that sperm undergo in the female reproductive tract to acquire fertilizing ability [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Ecto-nucleotidases distribution in human cyclic and postmenopausic endometrium

Aliagas

Vidal

Torrejón‐Escribano

et al. 2012

Purinergic Signalling

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Extracellular ATP and its hydrolysis product, adenosine, acting through specific receptors collectively named purinergic receptors, regulate female fertility by influencing the endometrial fluid microenvironment. There are four major groups of ecto-nucleotidases that control the levels of extracellular ATP and adenosine and thus their availability at purinergic receptors: ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases), ecto-nucleotide pyrophosphatase/phospho-diesterases (E-NPPs), ecto-5′-nucleotidase (5′NT), and alkaline phosphatases (APs). The aim of the present work is to characterize the expression and distribution of ecto-nucleotidases in human endometrium along the menstrual cycle and after menopause, to evaluate their potential utility as fertility markers. We examined proliferative, secretory and atrophic endometria from women without endometrial pathology undergoing hysterectomy. We show that the ecto-nucleotidases are mainly present at endometrial epithelia, both luminal and glandular, and that their expression fluctuates along the cycle and also changes after menopause. An important result was identifying NPP3 as a new biological marker of tubal metaplasia. Our results emphasize the relevance of the study of purinergic signaling in human fertility.

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“…Researchers involved in different fields of biomedical research are actively engaged in adenosine research due to its plethora of actions on different biologic systems (i.e., nervous, reproductive, cardiac, renal, hepatic, and respiratory systems) [18][19][20][21][22]. Adenosine, following its release, binds to adenosine receptors, which belong to a family of G protein coupled receptors (GPCRs) [23].…”

Section: Adenosine and Inflammationmentioning

confidence: 99%

Adenosine as an endogenous immunoregulator in cancer pathogenesis: where to go?

Kumar

2012

Purinergic Signalling

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Cancer is a chronic disease and its pathogenesis is well correlated with infection and inflammation. Adenosine is a purine nucleoside, which is produced under metabolic stress like hypoxic conditions. Acute or chronic inflammatory conditions lead to the release of precursor adenine nucleotides (adenosine triphosphate (ATP), adenosien diphosphate (ADP) and adenosine monophosphate (AMP)) from cells, which are extracellularly catabolized into adenosine by extracellular ectonucleotidases, i.e., CD39 or nucleoside triphosphate dephosphorylase (NTPD) and CD73 or 5′-ectonucleotidase. It is now well-known that adenosine is secreted by cancer as well as immune cells during tumor pathogenesis under metabolic stress or hypoxia. Once adenosine is released into the extracellular environment, it exerts various immunomodulatory effects via adenosine receptors (A 1 , A 2A , A 2B , and A 3 ) expressed on various immune cells (i.e., macrophages, myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, dendritic cells (DCs), T cells, regulatory T cell (T regs ), etc.), which play very important roles in the pathogenesis of cancer. This review is intended to summarize the role of inflammation and adenosine in the immunopathogenesis of tumor along with regulation of tumor-specific immune response and its modulation as an adjunct approach to tumor immunotherapy.

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Adenosine and Catecholamine Agonists Speed the Flagellar Beat of Mammalian Sperm by a Non-Receptor-Mediated Mechanism1

Cited by 22 publications

References 47 publications

Testicular Expression of Adora3i2 in Adora3 Knockout Mice Reveals a Role of Mouse A3Ri2 and Human A3Ri3 Adenosine Receptors in Sperm*

Testicular Expression of Adora3i2 in Adora3 Knockout Mice Reveals a Role of Mouse A3Ri2 and Human A3Ri3 Adenosine Receptors in Sperm*

Ecto-nucleotidases distribution in human cyclic and postmenopausic endometrium

Adenosine as an endogenous immunoregulator in cancer pathogenesis: where to go?

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