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

Mededovic, Samra; Fraser, Lynn R.

doi:10.1530/rep.1.00062

Cited by 23 publications

(28 citation statements)

References 45 publications

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“…FPP, adenosine and calcitonin have been shown to regulate membrane-associated adenylyl cyclase (mAC)/cAMP, first stimulating cAMP production in uncapacitated cells and then inhibiting cAMP in capacitated cells . This made it plausible that AII was also affecting cAMP production and this has now been confirmed in a recent study (Mededovic & Fraser 2004) where AII was shown to stimulate cAMP in both uncapacitated and capacitated spermatozoa. In that same study, AT1 receptors for AII were found to be located in the acrosomal cap region and along the whole of the flagellum in both mouse and human spermatozoa, consistent with the enhanced fertility observed in AII-treated mouse sperm suspensions (Fraser et al 2001); successful fertilization requires changes in both the sperm head and flagellum.…”

Section: Introductionmentioning

confidence: 65%

“…Although the study by Mededovic & Fraser (2004) confirmed that responses to AII involve a significant stimulation of cAMP production, it did not provide information on what elements might be involved in the signalling pathway. Current evidence suggests that the binding of FPP, calcitonin and adenosine to their respective receptors results in a G protein-mediated regulation of mAC, with the stimulatory responses involving Ga s and the inhibitory responses involving Ga i (possibly Ga i2 ); both Ga s and Ga i2 are found in the same regions as those receptors (Baxendale & Fraser 2003a).…”

Section: Introductionmentioning

confidence: 91%

“…Fraser et al 2001), in vitro fertilization (e.g. Fraser 1987) and tyrosine phosphorylation analysis (Adeoya-Osiguwa & Fraser 2000, Mededovic & Fraser 2004.…”

Section: Sperm Suspension Preparationmentioning

confidence: 99%

“…In that same study, AT1 receptors for AII were found to be located in the acrosomal cap region and along the whole of the flagellum in both mouse and human spermatozoa, consistent with the enhanced fertility observed in AII-treated mouse sperm suspensions (Fraser et al 2001); successful fertilization requires changes in both the sperm head and flagellum. AII-induced stimulation of cAMP production was associated with increases in protein tyrosine phosphorylation, as determined by immunolocalization of tyrosine phosphoproteins in the head and flagellum of individual cells and by Western blotting of sperm homogenates (Mededovic & Fraser 2004). There was evidence for capacitation-related differences both in the relative abundance of tyrosine phosphoproteins in the two compartments of intact spermatozoa and in the specific tyrosine phosphoproteins affected in response to AII.…”

Section: Introductionmentioning

confidence: 99%

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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: Introductionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 91%

“…Fraser et al 2001), in vitro fertilization (e.g. Fraser 1987) and tyrosine phosphorylation analysis (Adeoya-Osiguwa & Fraser 2000, Mededovic & Fraser 2004.…”

Section: Sperm Suspension Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mechanisms of action of angiotensin II on mammalian sperm function

Mededovic¹,

Fraser²

2005

Reproduction

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“…report ( 8 ), Ang II also inhibits adenylyl cyclase/cAMP in rat heart myocytes, aorta and hepatocytes. On the other hand, Ang II stimulates cAMP production in some tissue ( 9 ), and may enhance cAMP production via Ca 2+ /calmodulin ( 10 ). An increase in adenylyl cyclase/cAMP by a rise in available Ca 2+ has also been suggested ( 11 ).…”

mentioning

confidence: 99%

The Role of Tumor Necrosis Factor-α in Inducing Insulin Resistance in the Renin-Angiotensin System

2005

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Key Words : insulin resistance, renin-angiotensin system, tumor necrosis factor-S Recent evidences suggest that insulin resistance is one of the most important factors in cardiovascular diseases. Insulin resistance is also involved in metabolic syndrome, a clustering of atherosclerotic metabolic abnormalities. In the therapeutic strategies for metabolic syndrome, the relation between the action of insulin and the renin-angiotensin system (RAS) appears to be clinically important.Skeletal muscle and adipose tissue are known as insulinsensitive organs. Adipose tissue not only plays an important role in lipid metabolism, but also functions as an endocrine organ that produces bioactive molecules called adipokines, such as leptin, adiponectin and tumor necrosis factor-α (TNF-α ). On the other hand, skeletal muscle is known as a major cause of energy expenditure. Insulin resistance in skeletal muscle is observed in diabetic patients and animal models ( 1 − 3 ). TNF-α induces insulin resistance by inhibiting insulinmediated intracellular signaling ( 3 ). Moreover, recent reports have indicated that TNF-α is produced in skeletal muscle ( 4 − 6 ). Angiotensin II (Ang II) type 1 (AT 1 ) receptor blocker (ARB) has been shown to inhibit TNF-α production as well as insulin resistance ( 5 − 7 ). However, the mechanism of action of Ang II on regulation of TNF-α production has not been clear. In an article appearing in this issue of Hypertension Research (pp. 773 − 778), Yamaguchi et al . provide new evidence on the mechanism of action of RAS in TNF-α production in skeletal muscle using fructose-fed rats ( 8 ). They show that the tissue level of TNF-α in rat skeletal muscle was elevated by fructose-rich chow, and that this increase was inversely related with the level of cAMP. An ARB, olmesartan, inhibited the increase in TNF-α level as well as the change in cAMP level caused by fructose-rich chow. Their results suggest that TNF-α production is negatively regulated through cAMP in skeletal muscle. Moreover, they found that a blockade of AT 1 receptor decreased TNF-α production by increasing the level of cAMP.The possible involvement of AT 1 receptor signaling in the regulation of cAMP production is also an interesting subject. Most physiological actions of Ang II are mediated through AT 1 receptor. Ang II stimulation is often linked with phospholipase C activation, resulting in generation of diacylglycerol and inositol trisphosphate (IP3), activation of protein kinase C and intracellular Ca 2+ -mobilization through AT 1 receptor in the cardiovascular system and sympathetic neurons. However, as Yamaguchi et al . report ( 8 ), Ang II also inhibits adenylyl cyclase/cAMP in rat heart myocytes, aorta and hepatocytes. On the other hand, Ang II stimulates cAMP production in some tissue ( 9 ), and may enhance cAMP production via Ca 2+ /calmodulin ( 10 ). An increase in adenylyl cyclase/cAMP by a rise in available Ca 2+ has also been suggested ( 11 ). These findings suggest a complex and variable intracellular signaling of Ang II dependi...

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Mammalian sperm phosphodiesterases and their involvement in receptor‐mediated cell signaling important for capacitation

Baxendale

Fraser

2005

Molecular Reproduction Devel

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This study investigated the presence and function of intracellular cyclic nucleotide phosphodiesterases (PDEs) in mature mouse spermatozoa. PCR analysis detected gene transcripts for most of the 11 known PDE families in whole testis, but mainly for PDEs 1, 3, 6, and 8 in spermatozoa. Using specific antibodies, the strongest evidence was obtained for PDE proteins 1, 4, 6, 8, 10, and 11 in both sperm lysates and intact cells. These showed a range of subcellular localizations, with PDE 1A being primarily in the flagellum but PDEs 4D and 10A being in both the acrosomal region and the flagellum, similar to specific G proteins and adenylyl cyclases implicated in cAMP regulation during capacitation. In live spermatozoa, inhibitors selective for PDE 1 (MMPX) and 4 (rolipram) significantly increased cAMP over control levels but only rolipram significantly stimulated capacitation and in-vitro fertilizing ability; this suggests that compartmentalization has functional implications since only PDE 4 was abundant in both head and flagellum. Treatment of spermatozoa with CGS 21680, a stimulatory adenosine receptor agonist, significantly reduced cAMP-PDE activity at the same time-point when it causes increased cAMP. Thus, certain receptor-regulated cAMP processes in spermatozoa may be controlled by changes in both PDE and cyclase activities. In addition to demonstrating for the first time that some of the more recently discovered PDE isoforms, including PDE 6 (usually associated with the retina), are present in mature spermatozoa, this study provides clear evidence that the intracellular location of specific PDEs has important functional significance during capacitation and fertilization.

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

Cited by 23 publications

References 45 publications

Mechanisms of action of angiotensin II on mammalian sperm function

Mechanisms of action of angiotensin II on mammalian sperm function

The Role of Tumor Necrosis Factor-α in Inducing Insulin Resistance in the Renin-Angiotensin System

Mammalian sperm phosphodiesterases and their involvement in receptor‐mediated cell signaling important for capacitation

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