scholarly journals Desensitization of angiotensin II: effect on [Ca2+]i, inositol triphosphate, and prolactin in pituitary cells

2001 ◽  
Vol 280 (3) ◽  
pp. E462-E470 ◽  
Author(s):  
Arturo González Iglesias ◽  
Cecilia Suárez ◽  
Claudia Feierstein ◽  
Graciela Dı́az-Torga ◽  
Damasia Becu-Villalobos
Keyword(s):  
Inositol Phosphate ◽  
Prolactin Secretion ◽  
Inositol Triphosphate ◽  
Pituitary Cells ◽  
Partial Recovery ◽  
Ang Ii ◽  
Pretreated Group ◽  
Intracellular Ca ◽  
Heterologous Desensitization

Activation of pituitary angiotensin (ANG II) type 1 receptors (AT1) mobilizes intracellular Ca2+, resulting in increased prolactin secretion. We first assessed desensitization of AT1 receptors by testing ANG II-induced intracellular Ca2+ concentration ([Ca2+]i) response in rat anterior pituitary cells. A period as short as 1 min with 10−7 M ANG II was effective in producing desensitization (remaining response was 66.8 ± 2.1% of nondesensitized cells). Desensitization was a concentration-related event (EC50: 1.1 nM). Although partial recovery was obtained 15 min after removal of ANG II, full response could not be achieved even after 4 h (77.6 ± 2.4%). Experiments with 5 × 10−7 M ionomycin indicated that intracellular Ca2+ stores of desensitized cells had already recovered when desensitization was still significant. The thyrotropin-releasing hormone (TRH)-induced intracellular Ca2+ peak was attenuated in the ANG II-pretreated group. ANG II pretreatment also desensitized ANG II- and TRH-induced inositol phosphate generation (72.8 ± 3.5 and 69.6 ± 6.1%, respectively, for inositol triphosphate) and prolactin secretion (53.4 ± 2.3 and 65.1 ± 7.2%), effects independent of PKC activation. We conclude that, in pituitary cells, inositol triphosphate formation, [Ca2+]i mobilization, and prolactin release in response to ANG II undergo rapid, long-lasting, homologous and heterologous desensitization.

Intracellular translocation of PKC isoforms in canine pulmonary artery smooth muscle cells by ANG II

1998 ◽  
Vol 274 (2) ◽  
pp. L278-L288 ◽  
Author(s):  
Derek S. Damron ◽  
Hany S. Nadim ◽  
Sung Jin Hong ◽  
Ahmad Darvish ◽  
Paul A. Murray
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Inositol Phosphate ◽  
Ang Ii ◽  
Pkc Isoforms ◽  
Inositol Phosphate Production ◽  
Intracellular Ca ◽  
Pulmonary Artery Smooth Muscle ◽  
Pkc Ζ

Our goals were to identify the isoforms of protein kinase C (PKC) present in primary cultures of canine pulmonary artery smooth muscle cells (PASMCs) and to determine whether angiotensin II (ANG II) triggers translocation of specific PKC isoforms to discreet intracellular locations. Isoform-specific antibodies and Western blot analysis were utilized to identify the isoforms of PKC in PASMCs. Indirect immunofluorescence and confocal microscopy were used to examine the subcellular distribution of PKC isoforms. Inositol phosphate production was used to assess phospholipase C activation, and fura 2 was utilized to monitor intracellular Ca2+ concentration in response to ANG II. Six isoforms (α, δ, ε, ζ, ι/λ, and μ) of PKC were identified by Western blot analysis. Immunolocalization of 5 isoforms (α, δ, ζ, ι/λ, and μ) revealed a unique pattern of staining for each individual isoform. ANG II caused translocation of PKC-α from the cytosol to the nuclear envelope and of PKC-δ to the myofilaments. In contrast, cytosolic PKC-ζ did not translocate, but nuclear PKC-ζ was upregulated. Translocation of PKC-α and PKC-δ and upregulation of PKC-ζ in response to ANG II were blocked by the ANG II type 1-receptor antagonist losartan. In addition, ANG II stimulated inositol phosphate production and intracellular Ca2+concentration oscillations, which were blocked by losartan. Thus activation of ANG II type 1 receptors triggers the phosphoinositide signaling cascade, resulting in translocation or upregulation of specific PKC isoforms at discreet intracellular sites. The α and ζ isoforms may act to regulate nuclear events, whereas PKC-δ may be involved in modulating contraction via actions on the myofilaments.

Bradykinin stimulates phosphoinositide metabolism and prolactin secretion in rat anterior pituitary cells

1989 ◽  
Vol 2 (1) ◽  
pp. 47-53 ◽  
Author(s):  
T.H. Jones ◽  
B. L. Brown ◽  
P. R. M. Dobson
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Inositol Phosphate ◽  
Prolactin Secretion ◽  
Male Rats ◽  
Pituitary Cells ◽  
Phosphoinositide Metabolism ◽  
Phosphate Accumulation ◽  
Anterior Pituitary Cells ◽  
Inositol Phosphate Accumulation

ABSTRACT Bradykinin stimulated prolactin secretion from monolayer cultures of rat anterior pituitary cells, the stimulation being greater from the cells of male rats. This stimulated secretion was accompanied by a rise in total inositol phosphate accumulation, suggesting that the action of bradykinin is mediated by phosphoinositide hydrolysis. The increase in inositol phosphate accumulation was biphasic; a further sharp rise occurred when the concentration of bradykinin exceeded 1 μmol/l. This may indicate that bradykinin acts on other cell types in the pituitary gland. Bradykinin had no effect on growth hormone secretion from cells of normal pituitary glands, or on prolactin secretion and phosphoinositide metabolism in GH3 rat pituitary tumour cells. Bradykinin receptor antagonists (both B1 and B2) had no effect on either bradykinin-stimulated inositol phosphate accumulation or prolactin secretion. Kallikreins, the enzymes responsible for the generation of kinins, are known to be present in the adenohypophysis. Therefore, the results presented here would suggest that kinins may have a role as paracrine agents in the pituitary gland.

Maitotoxin increases inositol phosphates in rat anterior pituitary cells

1991 ◽  
Vol 6 (1) ◽  
pp. 95-99 ◽  
Author(s):  
M. A. Sortino ◽  
T. M. Delahunty ◽  
T. Yasumoto ◽  
M. J. Cronin
Keyword(s):  
Anterior Pituitary ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Cell Types ◽  
Calcium Stores ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Anterior Pituitary Cells ◽  
Intracellular Ca

ABSTRACT Maitotoxin is a potent marine poison that mobilizes calcium in most vertebrate cell types and accelerates secretion from anterior pituitary cells. It is not known whether voltage-sensitive calcium channels or other mechanisms initiate the effects of maitotoxin on anterior pituitary cells. Changes in intracellular Ca2+ levels may also be achieved by releasing internal calcium stores via inositol trisphosphate (InsP3). Indeed, maitotoxin rapidly increased inositol phosphate accumulation in a concentration-dependent manner. Calcium channel antagonists such as nifedipine and verapamil did not block this response nor did calcium-mobilizing agents (BAYk8644, A23187) mimic this effect. These data suggest that the mechanism by which maitotoxin acts at the pituitary may include the activation of an enzyme that produces the calcium-mobilizing signal InsP3.

Kallidin-induced stimulation of inositol phosphate production and prolactin release in rat anterior pituitary cells

1990 ◽  
Vol 123 (1) ◽  
pp. 37-42 ◽  
Author(s):  
T. Hugh Jones ◽  
Barry L. Brown ◽  
Pauline R. M. Dobson
Keyword(s):  
Anterior Pituitary ◽  
Inositol Phosphate ◽  
Prolactin Secretion ◽  
Male Rat ◽  
Pituitary Cells ◽  
Phosphoinositide Metabolism ◽  
Prolactin Release ◽  
Anterior Pituitary Cells ◽  
Inositol Phosphate Production ◽  
Stimulation Of

Abstract. The effect of the kinin, kallidin (lysyl-brady-kinin) on phosphoinositide metabolism and prolactin secretion was examined in male rat anterior pituitary cells in primary culture. Kallidin was found to stimulate both total inositol phosphate production and prolactin release. The stimulation of inositol phosphate was biphasic in nature, similar to that previously reported for bradykinin, although kallidin was approximately 10-fold more potent. Kallidin also stimulated prolactin secretion provoking a maximal stimulation of 193.0±11.1 (sem)% at 1 μmol/l. These findings suggest that kallidin-induced prolactin secretion may be mediated intracellularly by activation of phosphoinositide metabolism. The B2 receptor antagonists had no significant inhibitory effects on kallidin-stimulated phosphoinositide metabolism or prolactin release. The B1 agonist des-Arg9-bradykinin has previously been shown to have no effect on either parameter. As the effects of kinins on anterior pituitary cells do not appear to be mediated by either of the known kinin receptors, they may, therefore, act via a hitherto unrecognised kinin receptor.

Identification of G protein-coupled signaling pathways in cardiac fibroblasts: cross talk between Gq and Gs

2000 ◽  
Vol 278 (1) ◽  
pp. C154-C162 ◽  
Author(s):  
J. Gary Meszaros ◽  
Annette M. Gonzalez ◽  
Yuka Endo-Mochizuki ◽  
Sonia Villegas ◽  
Francisco Villarreal ◽  
...  
Keyword(s):  
G Protein ◽  
Cardiac Myocytes ◽  
Cross Talk ◽  
Inositol Phosphate ◽  
Cardiac Fibroblasts ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Adrenergic Response ◽  
Intracellular Ca ◽  
G Protein Coupled

Cardiac fibroblasts (CFs) are an important cellular component of myocardial responses to injury and to hypertrophic stimuli. We studied G protein-coupled receptors to understand how CFs integrate signals that activate Gq, Gs, and Gi. We predicted that the second messenger pathways present in CFs were distinct from those in cardiac myocytes and that unique signaling interactions existed in the CFs. ANG II, bradykinin, ATP, and UTP stimulated inositol phosphate (IP) production 2.2- to 7-fold. Each of these agonists elevated intracellular Ca2+ concentration ([Ca2+]i) via release from the intracellular Ca2+ storage compartment. Endothelin-1 (ET-1), carbachol, and norepinephrine failed to increase either IP production or [Ca2+]i. Although agonists that activated IP and Ca2+ transients had no effect on cAMP production when administered alone, these agents potentiated the β2-adrenergic response two- to fourfold. Hormones known to inhibit adenylyl cyclase activity in cardiac myocytes, such as ET-1 and carbachol, failed to lower the β-adrenergic response in fibroblasts. Order of potency and inhibitor data indicate that the functional receptor subtypes in these cells are β2, P2Y2, and AT1 for isoproterenol, ATP, and ANG II, respectively. We conclude that CFs express functional G protein-linked receptors that couple to Gq and Gs, with little or no coupling to Gi. The expression of receptors and their coupling to Gq- but not to Gi-linked responses distinguishes the signaling in CFs from that in myocytes. Furthermore, agonists that activate Gq in CFs potentiate stimulation of Gs, an example of signaling cross talk not observed in adult myocytes. These data suggest that G protein-mediated signaling in CFs is unique and may contribute to the specificity of hormone and drug action on individual cell types within the heart.

scholarly journals Angiotensin II-induced Ca2+mobilization and prolactin release in normal and hyperplastic pituitary cells

1998 ◽  
Vol 274 (3) ◽  
pp. E534-E540 ◽  
Author(s):  
Graciela Díaz-Torga ◽  
Arturo González Iglesias ◽  
Rita Achával-Zaia ◽  
Carlos Libertun ◽  
Damasia Becú-Villalobos
Keyword(s):  
Angiotensin Ii ◽  
Pituitary Tumors ◽  
Prolactin Secretion ◽  
Thymidine Uptake ◽  
Pituitary Cells ◽  
Ang Ii ◽  
Prolactin Release ◽  
Tumoral Cells

We evaluated the effects of angiotensin II (ANG II) and its antagonists on prolactin release, intracellular calcium ([Ca2+]i) mobilization, and [3H]thymidine uptake in cells from normal rat pituitaries and from estrogen-induced pituitary tumors. ANG II (10−7 to 10−9 M) increased prolactin release significantly in control and not in tumoral cells. In control cells, ANG II (10−6 to 10−9 M) produced an immediate spike of [Ca2+]ifollowed by a plateau. Spike levels rose significantly between 10−10 and 10−8 M ANG II, whereas the onset of the spike was retarded with decreasing concentrations. In tumoral cells, ANG II did not produce a spike phase even at 10−6 M. ANG II-induced prolactin release and calcium mobilization were blocked by losartan (AT1 receptor antagonist) and not by PD-123319 (AT2 antagonist). Finally, [3H]thymidine uptake was not modified by ANG II (10−7 to 10−10 M) or its antagonists in either group. Our results suggest that chronic in vivo estrogenic treatment alters in vitro pituitary response to ANG II. Alterations might function to limit excessive prolactin secretion of hypersecreting tumors. Besides, ANG II does not modify DNA synthesis in vitro of cells from normal or tumor-derived hypophyses.

Evidence that angiotensin II is a paracrine agent mediating gonadotrophin-releasing hormone-stimulated inositol phosphate production and prolactin secretion in the rat

1988 ◽  
Vol 116 (3) ◽  
pp. 367-371 ◽  
Author(s):  
T. H. Jones ◽  
B. L. Brown ◽  
P. R. M. Dobson
Keyword(s):  
Angiotensin Ii ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Prolactin Secretion ◽  
Male Rats ◽  
Pituitary Cells ◽  
Releasing Hormone ◽  
Phosphate Accumulation ◽  
Inositol Phosphate Accumulation ◽  
Gonadotrophin Releasing Hormone

ABSTRACT Gonadotrophin-releasing hormone (GnRH) stimulated the accumulation of inositol phosphates and prolactin secretion in anterior pituitary cells from young male rats. Saralasin ([Sar1,Ala8]-angiotensin II; a competitive antagonist of angiotensin II) inhibited the increase in both inositol phosphates and prolactin in a dose-dependent manner. Since angiotensin II has been shown to be a potent stimulus for inositol phosphate accumulation and prolactin secretion in the lactotroph, these findings suggest that angiotensin II acts as a paracrine agent, being released from the gonadotroph in response to GnRH and causing the lactotroph to release prolactin through an effect on phosphoinositide metabolism. The ability of GnRH to promote prolactin release was lost in pituitaries from older rats, and the increase in total inositol phosphate accumulation was less. These findings provide evidence of a physiological role for the presence of the renin–angiotensin system within the pituitary gland. J. Endocr. (1988) 116, 367–371

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

1999 ◽  
Vol 277 (3) ◽  
pp. E455-E463 ◽  
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.

Desensitization of norepinephrine receptor function is associated with G protein uncoupling in the rat aorta

1997 ◽  
Vol 273 (1) ◽  
pp. H279-H285 ◽  
Author(s):  
T. M. Seasholtz ◽  
H. Gurdal ◽  
H. Y. Wang ◽  
M. D. Johnson ◽  
E. Friedman
Keyword(s):  
G Protein ◽  
Inositol Phosphate ◽  
Rat Aorta ◽  
Ang Ii ◽  
Functional Responses ◽  
Heterologous Desensitization ◽  
Inositol Phosphate Accumulation ◽  
Beta Proteins ◽  
Infusion Of Norepinephrine ◽  
Gs Alpha

Infusion of norepinephrine (NE) in rats results in desensitization of NE-mediated aortic contraction and a reduction (55% at 1 and 10 microM) in NE-stimulated vascular inositol phosphate accumulations. The functional responses to angiotensin II (ANG II) were also reduced in the tissues of NE-infused animals. alpha 1-Adrenoceptor number determined by 2-[beta-(4-hydroxy-3-[125I]iodophenyl)-ethylaminomethyl]-tetralone ([125I]HEAT) binding and levels of G alpha or G beta proteins measured by immunoblot analyses were not changed in the aortic membranes of NE-infused animals. To determine whether desensitization is associated with receptor-G protein uncoupling, agonist-stimulated palmitoylation of G alpha proteins was measured. NE infusion decreased phenylephrine (1 microM)-stimulated [3H]palmitate incorporation into Gq alpha, Gs alpha, and Gi alpha proteins and ANG II (10 microM)-stimulated palmitoylation of Gq alpha and Gi alpha in aortic membranes. Phenylephrine- and ANG II-stimulated guanosine 5'-O-(3-[35S]thiotriphosphate) binding to Gq alpha was also decreased in the aortas of NE-infused animals. These results show that an infusion of NE causes heterologous desensitization of the contractile and inositol phosphate accumulation responses in the rat aorta and that these changes are mediated by an uncoupling of receptors from their G proteins.

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