Modulation of adenylyl cyclase by FPP and adenosine involves stimulatory and inhibitory adenosine receptors and g proteins

Fraser, Lynn R.; Adeoya-Osiguwa, Susan

doi:10.1002/(sici)1098-2795(199908)53:4<459::aid-mrd12>3.0.co;2-t

Cited by 51 publications

(79 citation statements)

References 35 publications

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“…The functional state of spermatozoa following experimental treatment was assessed using the CTC fluorescence assay as described by Fraser and Adeoya-Osiguwa (1999). An Olympus BX41 microscope (Olympus Optical Co (UK), London, UK) equipped with phase-contrast and epifluorescent optics was used to evaluate the cells, using the U-MWBV2 fluorescence cube (wide blue-violet) to assess CTC patterns.…”

Section: Ctc Fluorescence Analysismentioning

confidence: 99%

Mechanisms of action of angiotensin II on mammalian sperm function

Mededovic¹,

Fraser²

2005

Reproduction

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Angiotensin II (AII) stimulates capacitation and fertilizing ability in mammalian spermatozoa, with the binding of AII to its receptors resulting in stimulation of cAMP production in both uncapacitated and capacitated cells. This study investigated possible mechanisms whereby AII affects cAMP availability. The first question was whether extracellular Ca 21 is required for responses in mouse spermatozoa and, using chlortetracycline fluorescence analysis, it was clear that cells responded to AII only when the medium contained CaCl 2 , with both 90 mM and 1.80 mM supporting a significant acceleration of capacitation. Consistent with those results, AII significantly stimulated cAMP production in both CaCl 2 -containing media tested, the response being greater in that containing 1.80 mM. Several different agents that might affect the signalling pathway stimulated by AII were then evaluated in uncapacitated suspensions. Chlortetracycline analysis revealed that pertussis toxin abolished responses to AII, suggesting the involvement of an inhibitory Ga subunit; dideoxyadenosine, a specific membrane-associated adenylyl cyclase (mAC) P-site inhibitor, also blocked responses, suggesting involvement of an mAC. cAMP determinations confirmed that both reagents also abolished AII's stimulation of cAMP. In contrast, nifedipine, a Ca 21 channel blocker, did not inhibit AII's effects on spermatozoa. Finally, in capacitated suspensions, both pertussis toxin and dideoxyadenosine were again shown to block AII's stimulation of cAMP. These results suggest that responses to AII involve an inhibitory G protein and an mAC, but it is likely that AII -receptor coupling does not stimulate directly mAC but rather does so in an indirect manner, perhaps by altering the intracellular Ca 21 concentration.Reproduction (2005) 129 211-218

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Section: Ctc Fluorescence Analysismentioning

confidence: 99%

Mechanisms of action of angiotensin II on mammalian sperm function

Mededovic¹,

Fraser²

2005

Reproduction

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“…Current evidence indicates that FPP receptors elicit these responses by interacting with stimulatory and inhibitory adenosine receptors (Fraser & Adeoya-Osiguwa 1999). To test the hypothesis that AII affects AC/cAMP, uncapacitated mouse sperm suspensions were treated with CGS 21680, a specific agonist acting at stimulatory A 2A adenosine receptors and shown previously to stimulate AC/cAMP (Fraser & Adeoya-Osiguwa 1999), and with AII.…”

Section: Discussionmentioning

confidence: 99%

“…With uncapacitated suspensions, CGS 21680 was used; this is a specific agonist that binds to stimulatory A 2A adenosine receptors and stimulates cAMP production in uncapacitated spermatozoa (Fraser & Adeoya-Osiguwa 1999). With capacitated suspensions, CPA was used; this is a specific agonist that binds to inhibitory A 1 adenosine receptors and inhibits cAMP production in capacitated spermatozoa (Adeoya-Osiguwa & Fraser 2002).…”

Section: Series I: Localization Of At1 Receptorsmentioning

confidence: 99%

“…When low, ineffective concentrations of AII were used in combination with low concentrations of either FPP or calcitonin or with both, a significant response was obtained in uncapacitated cells, suggesting that the peptides were acting on the same signal transduction pathway. Since considerable evidence indicates that FPP, adenosine and calcitonin all regulate adenylyl cyclase (AC)/cAMP, initially stimulating cAMP production in uncapacitated cells and then inhibiting cAMP in capacitated cells (Adeoya-Osiguwa et al 1998, Fraser & Adeoya-Osiguwa 1999, Adeoya-Osiguwa & Fraser 2002, it was hypothesized that AII also acts via that pathway.…”

Section: Introductionmentioning

confidence: 99%

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Angiotensin II stimulates cAMP production and protein tyrosine phosphorylation in mouse spermatozoa

Mededovic

Fraser

2004

Reproduction

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Angiotensin II (AII), found in seminal plasma, has been shown to stimulate capacitation in uncapacitated mammalian spermatozoa. The present study investigated the location of AII receptors on spermatozoa and AII's mechanism of action. AT1 type receptors for AII are present on the acrosomal cap region and along the whole of the flagellum of both mouse and human spermatozoa. Because combinations of low concentrations of AII and either calcitonin or fertilization-promoting peptide (FPP), both known to regulate the adenylyl cyclase (AC)/cAMP signal transduction pathway, elicited a significant response, this study investigated the hypothesis that these peptides act on the same pathway. AII was shown to significantly stimulate cAMP production in both uncapacitated and capacitated mouse spermatozoa and this was associated with increases in protein tyrosine phosphorylation. Using an anti-phosphotyrosine antibody to visualize the location of tyrosine phosphoproteins within individual cells, AII significantly stimulated phosphorylation within 20 min in both the head, especially in the acrosomal cap region, and the flagellum, especially in the principal piece, of uncapacitated mouse spermatozoa; combined AII 1 FPP was stimulatory within 5 min. In addition, Western blotting revealed that AII stimulation increased phosphorylation in a number of tyrosine phosphoproteins in both uncapacitated and capacitated mouse spermatozoa, with some being altered only in the latter category of cells. These results support the hypothesis that AII stimulates AC/cAMP in mammalian spermatozoa.

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“…20,21 Spermatozoa were observed using an Olympus BX40 microscope equipped with a wide blue-violet excitation cube (U-MWBV), BX-FLA excitation filters (set at 400-440 nM) and a DM455 dichroic mirror. In each sample, 100 cells were classified as having one of three staining patterns: Full, fluorescence over the whole head, characteristic of uncapacitated, acrosome-intact spermatozoa; Band, fluorescence-free band in the postacrosomal region, indicating capacitated, acrosome-intact cells; and Acrosome Reacted (AR), dull or absent fluorescence, characteristic of capacitated, acrosome-reacted spermatozoa.…”

Section: Sperm Capacitancementioning

confidence: 99%

Phosphodiesterase 11 (PDE11) regulation of spermatozoa physiology

et al. 2005

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Fertilization is well correlated with sperm concentration, rate of forward motility, and percentage of live, uncapacitated ejaculated spermatozoa, which is regulated in part by cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Phosphodiesterases (PDEs) hydrolyze cyclic nucleotides to their corresponding monophosphates, thereby counterbalancing the activities of cAMP and cGMP, and PDE11 is highly expressed in the testis, prostate, and developing spermatozoa. However, a physiological role of PDE11 is not known. We generated PDE11 knockout (PDE11 À/À ) mice to investigate the role of PDE11 in spermatozoa physiology. Ejaculated sperm from PDE11 À/À mice displayed reduced sperm concentration, rate of forward progression, and percentage of live spermatozoa. Pre-ejaculated sperm from PDE11 À/À mice displayed increased premature/spontaneous capacitance. These data are consistent with human data and suggest a role for PDE11 in spermatogenesis and fertilization potential. This is the first phenotype described for the PDE11 À/À mouse and the first report of a physiological role for PDE11.

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Modulation of adenylyl cyclase by FPP and adenosine involves stimulatory and inhibitory adenosine receptors and g proteins

Cited by 51 publications

References 35 publications

Mechanisms of action of angiotensin II on mammalian sperm function

Mechanisms of action of angiotensin II on mammalian sperm function

Angiotensin II stimulates cAMP production and protein tyrosine phosphorylation in mouse spermatozoa

Phosphodiesterase 11 (PDE11) regulation of spermatozoa physiology

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