Mechanisms of action of angiotensin II on mammalian sperm function

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 Ca2+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 CaCl2, with both 90 μM and 1.80 mM supporting a significant acceleration of capacitation. Consistent with those results, AII significantly stimulated cAMP production in both CaCl2-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 Gα subunit; dideoxyadenosine, a specific membrane-associated adenylyl cyclase (mAC) P-site inhibitor, also blocked responses, suggesting involvement of an mAC. cAMP determinations con-firmed that both reagents also abolished AII’s stimulation of cAMP. In contrast, nifedipine, a Ca2+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 Ca2+concentration.

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Angiotensin II potentiates adrenocorticotrophic hormone-induced cAMP formation in bovine adrenal glomerulosa cells through a capacitative calcium influx

Biochemical Journal ◽

10.1042/bj3300021 ◽

1998 ◽

Vol 330 (1) ◽

pp. 21-27 ◽

Cited By ~ 36

Author(s):

M. Muriel BURNAY ◽

B. Michel VALLOTTON ◽

M. Alessandro CAPPONI ◽

F. Michel ROSSIER

Keyword(s):

Angiotensin Ii ◽

Calcium Channels ◽

Adenylyl Cyclase ◽

Adrenocorticotrophic Hormone ◽

Camp Production ◽

Glomerulosa Cells ◽

Camp Formation ◽

Voltage Operated Calcium Channels ◽

Ca2 Channels ◽

Stimulation Of

Angiotensin II (AngII) plays a crucial role in the control of aldosterone biosynthesis in adrenal glomerulosa cells through the stimulation of two distinct Ca2+ entry pathways: (1) opening of voltage-operated calcium channels, and (2) activation of a capacitative Ca2+ entry that is dependent on calcium release from intracellular pools. Adrenocorticotrophic hormone (ACTH), on the other hand, a major hormonal regulator of steroidogenesis, induces an increase in intracellular cAMP through the activation of a G-protein-coupled adenylyl cyclase. Recent studies have demonstrated that the rise in cAMP induced by ACTH can be potentiated by AngII in bovine glomerulosa cells. The aim of the present study was to investigate the mechanism of AngII action on ACTH-induced cAMP production. In primary cultures of bovine glomerulosa cells, we found that AngII (100 nM), which had no effect by itself on cAMP production, significantly potentiated maximal ACTH-induced cAMP formation in the presence of extracellular calcium (1.2 mM). In contrast, in the absence of extracellular calcium, AngII did not affect ACTH-induced cAMP production. These results suggest that calcium entry into the cell plays an important role in the activation of the cyclase by AngII. The inhibition of voltage-operated calcium channels by nicardipine, a dihydropyridine calcium antagonist blocking both low-threshold (T-type) and high-threshold (L-type) Ca2+ channels, did not significantly affect the potentiating effect of AngII. Moreover, the cAMP response to ACTH was insensitive to activation of these Ca2+ channels induced by potassium ions and, even when cytosolic free-calcium concentration ([Ca2+]c) was kept elevated with the Ca2+ ionophore, ionomycin, no stimulation of adenylyl cyclase was observed at concentrations of [Ca2+]c up to 640 nM. In contrast, thapsigargin, an activator of capacitative Ca2+ influx, mimicked the potentiating effect of AngII on ACTH-induced cAMP formation. In agreement with the characteristics of cAMP modulation by Ca2+ in these cells, the presence of type III adenylyl cyclase was observed by immunodetection in bovine glomerulosa cell membranes. In conclusion, these data suggest a tight coupling between the capacitative Ca2+ influx induced upon stimulation by either AngII or thapsigargin and a calcium-sensitive isoform of adenylyl cyclase, probably type III, in bovine glomerulosa cells.

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Effect of substance P and neurokinin A on rat parietal cell function

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1990.259.4.g646 ◽

1990 ◽

Vol 259 (4) ◽

pp. G646-G654

Author(s):

W. Schepp ◽

J. Schmidtler ◽

C. Tatge ◽

V. Schusdziarra ◽

M. Classen

Keyword(s):

Substance P ◽

Parietal Cell ◽

Pertussis Toxin ◽

Cell Function ◽

Inhibitory Effect ◽

Parietal Cells ◽

Neurokinin A ◽

Cholinergic Stimulation ◽

Camp Production ◽

Stimulation Of

In enzymatically dispersed enriched (76%) rat parietal cells we studied the effect of substance P on acid sequestration as indirectly measured by [14C]aminopyrine accumulation. Substance P (10(-8)-10(-5) M) had no effect on basal [14C]aminopyrine accumulation. Yet, the peptide reduced the response to histamine and to the postreceptor agonists forskolin and dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP). Inhibition by substance P followed noncompetitive kinetics and reduced stimulated parietal cell function by up to 45% at 10(-5) M. The antagonist [D-Pro2, D-Trp7,9]-substance P at 10(-5) M partly reversed the inhibitory effect of substance P. Cholinergic stimulation of [14C]aminopyrine accumulation was not reduced by substance P. Neurokinin A, another tachykinin that is structurally related to substance P, was of comparable potency and efficacy in reducing [14C]aminopyrine accumulation in response to histamine, forskolin, and DBcAMP. Inhibition of forskolin- or DBcAMP-induced [14C]aminopyrine accumulation persisted in the presence of 10(-5) M ranitidine. Inhibition by substance P and neurokinin A of the response to histamine was not sensitive to pertussis toxin. Both tachykinins failed to reduce histamine- and forskolin-stimulated cAMP production. Our data suggest that substance P and neurokinin A exert a direct effect on rat parietal cells. They attenuate histamine-stimulated acid sequestration at an intracellular step that is distal to the adenylate cyclase and that does not involve pertussis toxin-sensitive GTP-binding proteins.

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EP4Prostanoid Receptor Coupling to a Pertussis Toxin-Sensitive Inhibitory G Protein

Molecular Pharmacology ◽

10.1124/mol.105.017749 ◽

2005 ◽

Vol 69 (1) ◽

pp. 5-10 ◽

Cited By ~ 77

Author(s):

Hiromichi Fujino ◽

John W. Regan

Keyword(s):

G Protein ◽

Pertussis Toxin ◽

Receptor Coupling ◽

Inhibitory G Protein

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cAMP-dependent ACTH secretagogues facilitate corticotropin releasing activity of angiotensin II on rat anterior pituitary cells in vitro

Acta Endocrinologica ◽

10.1530/acta.0.1140118 ◽

1987 ◽

Vol 114 (1) ◽

pp. 118-123 ◽

Cited By ~ 1

Author(s):

P. Schoenenberg ◽

R. C. Gaillard ◽

P. Kehrer ◽

A. F. Muller

Keyword(s):

Angiotensin Ii ◽

Anterior Pituitary ◽

Fold Increase ◽

Pituitary Cells ◽

Camp Production ◽

Camp Pathway ◽

Anterior Pituitary Cells ◽

Stimulation Of ◽

Acth Release

Abstract. Both arginine vasopressin (AVP) and angiotensin II (All) potentiate the corticotropin-releasing activity of CRF41 via a potentiation of CRF41-induced cAMP production. In perfused rat anterior pituitary cells, AII (10−8 mol) showed a transitory 2-fold increase in its ACTH-releasing activity, when tested after application extract of rat stalk median eminence. In order to determine whether this facilitating effect on All corticotropin-releasing activity occurred through cAMP-dependent mechanisms, the ACTH-releasing activity of All was tested after stimulation with CRF41, AVP or forskolin, three secretagogues with known effects on cAMP production. When given 16 min after CRF41, 10 μg/l, All (10−8 mol) showed a significant increase (210%) in its ACTH-releasing activity, which returned to the normal level when All-stimulation was repeated at 32 min (121%) and 48 min (100%). Similarly, forskolin, 3 × 10−6 mol, produced a significant transitory increase (208%) in the subsequent All-induced ACTH release whereas AVP, 10 μg/l and 100 μg/l, had no effect on the following ACTH response to All. These results suggest that the All-induced ACTH secretion – which is cAMP independent – nevertheless may be modulated by previously stimulation of the cAMP pathway.

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PTH elevates inositol polyphosphates and diacylglycerol in a rat osteoblast-like cell line

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1988.255.5.e660 ◽

1988 ◽

Vol 255 (5) ◽

pp. E660-E667 ◽

Cited By ~ 1

Author(s):

R. Civitelli ◽

I. R. Reid ◽

S. Westbrook ◽

L. V. Avioli ◽

K. A. Hruska

Keyword(s):

Cell Line ◽

Pertussis Toxin ◽

Inositol Phosphates ◽

Cytosolic Calcium ◽

Camp Production ◽

Inositol Polyphosphates ◽

Rapid Stimulation ◽

Rat Osteoblast ◽

Umr 106 ◽

Stimulation Of

Parathyroid hormone (PTH)-stimulated signal transduction through mechanisms alternate to adenosine 3',5'-cyclic monophosphate (cAMP) production were studied in UMR 106-01 cells, a cell line with an osteoblastic phenotype. PTH produced transient, dose-related increases in cytosolic calcium [( Ca2+]i), inositol trisphosphates, and diacylglycerol (DAG). Both inositol 1,4,5-trisphosphate (Ins-1,4,5P3) and inositol 1,3,4-trisphosphate (Ins-1,3,4P3) production were rapidly stimulated by PTH. Consistent with the production of Ins-1,3,4P3, rapid stimulation of late eluting inositol tetrakisphosphate was observed. The effects on the inositol phosphates were induced rapidly, consistent with roles as signals for changes in [Ca2+]i. In saponin-permeabilized UMR 106-01 cells, Ins-1,4,5P3 stimulated 45Ca release from a nonmitochondrial intracellular pool. Thus the hypothesis that PTH-stimulated Ins-1,4,5P3 production initiates Ca2+ release and contributes to transient elevations of [Ca2+]i is supported. Pretreatment of UMR 106-01 cells with pertussis toxin had no effect on PTH stimulation of inositol phosphates. Pertussis toxin reduced PTH-stimulated elevations of [Ca2+]i, but cAMP analogues had an even greater effect than pertussis toxin. These data suggest that stimulation of cAMP production during PTH stimulation may negatively affect production of rises in [Ca2+]i during PTH stimulation. The inactivation of the inhibitory G protein of adenylate cyclase by pertussis toxin could explain its action similar to cAMP analogues. Cyclic nucleotides diminish the effects of PTH on [Ca2+]i, probably interacting on a biochemical step subsequent to or independent of Ins-1,4,5P3 release.

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Calcium influx and intracellular stores in angiotensin II stimulation of normal and hyperplastic pituitary cells

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1999.277.3.e455 ◽

1999 ◽

Vol 277 (3) ◽

pp. E455-E463 ◽

Cited By ~ 3

Author(s):

Arturo Gonzalez Iglesias ◽

Graciela Diaz-Torga ◽

Victoria Lux-Lantos ◽

Carlos Libertun ◽

Damasia Becu-Villalobos

Keyword(s):

Plasma Membrane ◽

Angiotensin Ii ◽

Calcium Influx ◽

Pituitary Cells ◽

Ang Ii ◽

Rat Pituitary ◽

Inositol 1,4,5 Trisphosphate ◽

Intracellular Ca ◽

Rat Pituitary Cells ◽

Stimulation Of

In rat pituitary cells from estrogen-induced hyperplasia, angiotensin II (ANG II) does not evoke a clear spike elevation of intracellular Ca2+concentration ([Ca2+]i) but induces a plateau increase. The present work was undertaken to establish whether this difference was related to a differential participation of intracellular and/or plasma membrane Ca2+ channels. We first tested the effect of 10 nM ANG II on [Ca2+]iin the absence of extracellular Ca2+ in cells depolarized with 25 mM K+ or in the presence of blockers of L-type voltage-sensitive Ca2+ channels (VSCC). These treatments did not alter spike elevation in [Ca2+]iin controls but reduced plateau levels in hyperplastic cells. Intracellular Ca2+ stores were similar in both groups, as assessed by thapsigargin treatment, but this drug abolished spike increase in controls and scarcely modified plateau levels in hyperplastic cells. Finally, inositol trisphosphate (InsP3) production in response to ANG II was significantly higher in control cells. We conclude that the observed plateau rise in hyperplastic cells results mainly from Ca2+ influx through VSCC. In contrast, in control cells, the ANG II-induced spike increase in [Ca2+]iresults from mobilization of Ca2+from thapsigargin-sensitive internal channels, activated by higher inositol 1,4,5-trisphosphate generation.

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Cdc42 activity is essential for the interplay between cAMP/PKA pathway and CatSper function

10.1101/2020.08.24.264739 ◽

2020 ◽

Author(s):

Guillermina M. Luque ◽

Xinran Xu ◽

Ana Romarowski ◽

María G. Gervasi ◽

Gerardo Orta ◽

...

Keyword(s):

Regulatory Mechanism ◽

Camp Production ◽

Mammalian Sperm ◽

Mechanistic Insight ◽

Complex Regulation ◽

Principal Piece ◽

Pka Pathway ◽

Dependent Pathway ◽

Insight Into ◽

Stimulation Of

AbstractSperm acquire the ability to fertilize in a process called capacitation and undergo hyperactivation, a change in the motility pattern, which depends on Ca2+ transport by CatSper channels. CatSper is essential for fertilization and it is subjected to a complex regulation that is not fully understood. Here, we report that similar to CatSper, Cdc42 distribution in the principal piece is confined to four linear domains and this localization is disrupted in CatSper1-null sperm. Cdc42 inhibition impaired CatSper activity and other Ca2+-dependent downstream events resulting in a severe compromise of the sperm fertilizing potential. We also demonstrate that Cdc42 is essential for CatSper function by modulating cAMP production by sAC, providing a new regulatory mechanism for the stimulation of CatSper by the cAMP/PKA-dependent pathway. These results reveal a broad mechanistic insight into the regulation of Ca2+ in mammalian sperm, a matter of critical importance in male infertility as well as in contraception.

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