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S Kapas

Publications and source records attributed to S Kapas.

At least 73 records · Page 4Linked to original sources
PubMed1994

Internalization of the type I angiotensin II receptor (AT1) is required for protein kinase C activation but not for inositol trisphosphate release in the angiotensin II stimulated rat adrenal zona glomerulosa cell.

A specific antibody, 6313/G2, to the N-terminus of the angiotensin II type I (AT1) receptor causes retention of the AT1 receptor in the plasma membrane of rat adrenal zona glomerulosa cells and stimulates steroidogenesis and inositol trisphosphate (IP3) release. Its effects are not significantly additive with those of angiotensin. In contrast, 6313/G2 completely inhibits angiotensin induced translocation of protein kinase C to the membrane fraction, although alone it has no effect. The data suggest that IP3 linked events, such as steroidogenesis, do not require receptor internalization, but protein kinase C activation does. They also confirm that protein kinase C activation is not required for stimulation of steroidogenesis in rat dispersed glomerulosa cells.

Aldosterone↗
PubMed1994

Endothelin-1 release from the isolated perfused rat adrenal gland is elevated acutely in response to increasing flow rates and ACTH(1-24).

Data obtained from the perfused rat adrenal gland demonstrated that immunoreactive endothelin (ET) was rapidly released in response to both mechanically increased flow rates through the gland and the increase in flow rate caused by ACTH(1-24). There was a good temporal correlation between the release of immunoreactive ET and increasing flow rates through the isolated perfused adrenal gland, which was detected immediately and was continuous throughout the period during which flow rate was elevated. The effects of exogenously administered ET were found to be transient; it caused a decrease in vascular perfusion lasting < 30 min. In these respects ET fulfils the requirements for it to be a short term paracrine mediator of adrenocortical function.

Adrenal Glands↗
PubMed1994

The role of neuropeptides in the regulation of adrenal vascular tone: effects of vasoactive intestinal polypeptide, substance P, neuropeptide Y, neurotensin, Met-enkephalin, and Leu-enkephalin on perfusion medium flow rate in the intact perfused rat adrenal.

There is evidence that adrenal blood flow may be regulated in part by neuropeptides released from the capsular region of the adrenal gland in response to splanchnic nerve stimulation. The present study investigated the effects of various neuropeptides on the rate of perfusion medium flow through an intact in situ perfused rat adrenal preparation. Vasoactive intestinal polypeptide (VIP) had the greatest effect, causing a 136% increase in flow at the highest dose used (10 nmol in a 200 microliters bolus). Of the other peptides tested Met-enkephalin caused a 50% increase in flow, and the others (Leu-enkephalin, neurotensin and substance P) had only a minor effect, increasing perfusion medium flow rate by no more than around 35%. Neuropeptide Y, in contrast, caused a significant decrease in perfusion medium flow rate: the maximum effect was a 30% decrease with a dose of 1 nmol in a 200 microliters bolus. The significance of this observation awaits elucidation. It is clear from the actions of the neuropeptides tested that they may have a significant role in the regulation of adrenal blood flow. In view of the findings of other authors: that VIP is released in response to splanchnic nerve stimulation, and that it is specifically localised in the capsular region of the adrenal, it seems most likely that VIP is the major peptide involved in mediating the increased adrenal blood flow following splanchnic nerve stimulation.

Adrenal Glands↗
PubMed1994

The role of neuropeptides in the regulation of adrenal zona fasciculata/reticularis function. Effects of vasoactive intestinal polypeptide, substance P, neuropeptide Y, Met- and Leu-enkephalin and neurotensin on corticosterone secretion in the intact perfused rat adrenal gland in situ.

There is much evidence to suggest that glucocorticoid secretion may be influenced by the splanchnic innervation to the adrenal gland, and that this effect may be mediated by neuropeptides. The present studies investigated the effects of several neuropeptides on corticosterone secretion by the intact perfused rat adrenal gland in situ. Both vasoactive intestinal polypeptide and Met-enkephalin caused a dose-dependent increase in corticosterone secretion, with a maximum response of 450% and 370% increment in corticosterone respectively. Of the other peptides tested, Leu-enkephalin, substance P and neurotensin all stimulated corticosterone secretion, with a maximum response of around 160% increase in each case. Neuropeptide Y on the other hand, had only a minor effect, which was only apparent over a small dose range. These results support the theory that adrenal neuropeptides may have a role in the regulation of glucocorticoid secretion.

Adrenal Glands↗
PubMed1994

Alpha-melanocyte-stimulating hormone-induced inhibition of angiotensin II receptor-mediated events in the rat adrenal zona glomerulosa.

It is well established that ACTH and angiotensin II (Ang II) stimulate aldosterone secretion from rat adrenal zona glomerulosa cells in vitro and mediate their steroidogenic effects via the cyclic AMP (cAMP) pathway and phosphoinositide turnover respectively. alpha-MSH also stimulates aldosterone secretion from zona glomerulosa cells in vitro, and recent studies from our laboratory have shown that its steroidogenic effects are mediated by increases in inositol 1,4,5-trisphosphate (IP3) production. alpha-MSH also stimulates adenylyl cyclase activity, but only at concentrations that are supramaximal for stimulation of steroidogenesis. The observation that alpha-MSH-stimulated IP3 accumulation declines as the activity of adenylyl cyclase increases prompted further studies on the interactions of cAMP and phosphoinositide production. The effects of alpha-MSH and ACTH on Ang II-stimulated steroidogenesis and IP3 accumulation were studied. On addition of increasing concentrations of ACTH, both the aldosterone and IP3 responses to Ang II were significantly inhibited; however, only high concentrations of alpha-MSH achieved this effect. These results suggest that cAMP or a cAMP-dependent event is able to inhibit phospholipase C activity. This hypothesis was tested by measuring IP3 production in Ang II-stimulated zona glomerulosa cells exposed to two different concentrations of alpha-MSH: 1 nmol/l, which stimulates the generation of IP3, and 1 mumol/l, which activates adenylyl cyclase. It was found that this high concentration of alpha-MSH significantly inhibited Ang II-stimulated aldosterone secretion and IP3 levels. In addition, alpha-MSH reduced 125I-labelled Ang II binding to rat adrenal zona glomerulosa cells.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

The role of neuropeptides in the regulation of adrenal zona glomerulosa function: effects of substance P, neuropeptide Y, neurotensin, Met-enkephalin, Leu-enkephalin and corticotrophin-releasing hormone on aldosterone secretion in the intact perfused rat adrenal.

A range of neuropeptides has been identified in the adrenal glands of many mammalian species. In many cases these peptides have been located in nerves supplying the adrenal cortical cells, or within clusters of chromaffin cells within the zona glomerulosa. The function of these neuropeptides has yet to be determined, but from their location within the gland it is clearly possible that they may have a role in the regulation of aldosterone secretion. The effects of Met-enkephalin, Leu-enkephalin, neuropeptide Y, substance P, corticotrophin-releasing hormone (CRH) and neurotensin on aldosterone secretion were investigated using the intact perfused rat adrenal gland in situ. All the peptides tested, except CRH, caused a significant increase in aldosterone secretion over the dose range of 1 pmol to 10nmol, with a maximum response of about a twofold increase in secretion. Met-enkephalin, however, at a dose of 10 nmol caused a 350% increase in aldosterone secretion, a response comparable with that seen in response to angiotensin II in this preparation. These results suggest that, while substance P, neuropeptide Y, neurotensin and Leu-enkephalin all have the capacity to cause modest increases in the rate of steroid secretion by the zona glomerulosa, these neuropeptides probably do not have a major role in the acute regulation of aldosterone secretion, at least under basal conditions. Met-enkephalin, on the other hand, was a more potent stimulus to aldosterone secretion, and thus may have a role in the control of aldosterone secretion.

Aldosterone↗
PubMed1993

Functional characterization of the cloned human ACTH receptor: impaired responsiveness of a mutant receptor in familial glucocorticoid deficiency.

The putative ACTH receptor gene has been identified on the basis of its tissue specific expression, structure, and limited expression data. We have expressed this gene in COS-7 cells and measured cAMP production in response to ACTH. An EC50 of 5.5 x 10(-9) M for ACTH (1-24) was determined. The S74I mutant ACTH receptor gene that associates with the syndrome of familial glucocorticoid deficiency had an EC50 of 67 x 10(-9) M. This discrepancy is consistent with the clinical data, and supports the hypothesis that this point mutation could account for the syndrome.

Adrenocorticotropic Hormone↗
PubMed1992

Studies on the intracellular mechanism of action of alpha-melanocyte-stimulating hormone on rat adrenal zona glomerulosa.

The intracellular mechanisms of action of alpha-MSH in rat adrenocortical cells were examined. When rat adrenal capsule (largely glomerulosa) cells were stimulated with a range of concentrations of alpha-MSH there was significant stimulation of aldosterone secretion at 10(-10) mol/l, although cyclic AMP was not increased until high concentrations of alpha-MSH were used (10(-6) mol/l and above). However, cells incubated with ACTH showed an increase in aldosterone secretion at 10(-11) mol/l and levels of cyclic AMP were elevated at 10(-9) mol ACTH/l. When rat adrenal whole capsules were incubated with alpha-MSH, membrane-bound protein kinase C (PKC) activity was increased and cytosolic enzyme activity decreased, showing PKC activation. Stimulation with angiotensin II also induced translocation of PKC activity, but ACTH did not. When [3H]inositol-loaded glomerulosa cells were stimulated with alpha-MSH there was significant generation of [3H]inositol trisphosphate (IP3) at concentrations of alpha-MSH which stimulated secretion of aldosterone. Significantly increased levels of [3H]IP3 were also measured when loaded cells were exposed to angiotensin II. ACTH did not cause any significant stimulation of [3H]IP3 production at any concentration used. These results indicate that activation of PKC and phospholipase C is important in modulating the steroidogenic effect of alpha-MSH.

Adrenocorticotropic Hormone↗
PubMed1992

Vasoactive intestinal peptide stimulation of aldosterone secretion by the rat adrenal cortex may be mediated by the local release of catecholamines.

The effects of vasoactive intestinal peptide (VIP) on adrenocortical function were investigated using several different preparations of adrenocortical tissue. VIP caused a significant increase in perfusion medium flow rate and in aldosterone and corticosterone secretion by the isolated perfused rat adrenal gland, with a threshold of 1 pmol in 200 microliters, but did not affect basal steroid secretion by collagenase-dispersed adrenocortical cells at any concentration used, from 10 pmol/l to 10 mumol/l. The presence of VIP (100 nmol/l) had no significant effect on the response of zona glomerulosa cells to stimulation by ACTH at any concentration. In incubations of intact adrenal capsular tissue, VIP (10 mumol/l) caused a significant stimulation of aldosterone secretion, and also induced a significant release of adrenaline into the incubation medium. Addition of (-)alprenolol (100 nmol/l), a beta-adrenergic antagonist, to the incubation medium significantly attenuated the response of capsular tissue to VIP. It is concluded that the effects of VIP on aldosterone, which are only seen when the architecture of the zona glomerulosa is preserved, may be mediated by the local release of adrenaline.

Adrenal Cortex↗
PubMed1991

The relationship between adrenal vascular events and steroid secretion: the role of mast cells and endothelin.

The actions of ACTH on the adrenal cortex are known to be 2-fold. In addition to increased steroidogenesis, ACTH also causes marked vasodilation, reflected by an increased rate of blood flow through the gland. Our studies, using the in situ isolated perfused rat adrenal preparation, have shown that zona fasciculata function and corticosterone secretion are closely related to vascular events, with an increase in perfusion medium flow rate causing an increase in corticosterone secretion, in the absence of any known stimulant. These observations give rise to two important questions: how does ACTH stimulate blood flow; and how does increased blood (or perfusion medium) flow stimulate steroidogenesis? Addressing the first question, we have recently identified mast cells in the adrenal capsule, and shown that Compound 48/80, a mast cell degranulator, mimics the actions of ACTH on adrenal blood flow and corticosterone secretion. We have also demonstrated an inhibition of the adrenal vascular response to ACTH in the presence of disodium cromoglycate, which prevents mast cell degranulation. We conclude, therefore, that ACTH stimulates adrenal blood flow by its actions on mast cells in the adrenal capsule. Addressing the second question, we looked at the role of endothelin in the rat adrenal cortex. Endothelin 1, 2 and 3 caused significant stimulation of steroid secretion by collagenase dispersed cells from both the zona glomerulosa and the zona fasciculata. A sensitive response was seen, with significant stimulation at an endothelin concentration of 10(-13) mol/l or lower. Endothelin secretion by the in situ isolated perfused rat adrenal gland was measured using the Amersham assay kit. Administration of ACTH (300 fmol) caused an increase in the rate of immunoreactive endothelin secretion, from an average of 28.7 +/- 2.6 to 52.6 +/- 6 fmol/10 min (P less than 0.01, n = 5). An increase in immunoreactive endothelin secretion was also seen in response to histamine, an adrenal vasodilator, which stimulates corticosterone secretion in the intact gland, but has no effect on collagenase-dispersed cells. From these data we conclude that endothelin may mediate the effects of vasodilation on corticosterone secretion, and this mechanism may explain some of the differences in response characteristics between the intact gland and dispersed cells.

Adrenal Cortex↗
PubMed1991

Effect of the endothelins on aldosterone secretion by rat zona glomerulosa cells in vitro.

Endothelins are thought to be involved in the local regulation of blood flow and tissue function. These experiments were carried out to investigate the possible role of endothelins in the control of aldosterone secretion by the rat adrenal. Suspensions of zona glomerulosa cells were prepared by collagenase digestion of capsular tissue, and incubated in the presence of increasing concentrations of endothelin. Aldosterone was measured by RIA. All three peptides caused a dose-dependent increase in the secretion rate of aldosterone by zona glomerulosa cells. The minimum concentration of peptide required to give a significant response was 10(-14) mol/l for endothelins 2 and 3 and 10(-13) mol/l for endothelin 1. At a concentration of 10(-7) mol/l endothelin 2 elicited a 20-fold increase over basal aldosterone secretion, while both endothelins 1 and 3 elicited a 30-fold increase (P less than 0.001 in all cases). These results show that the endothelins are potent stimulators of aldosterone secretion, and suggest that these peptides may have a role in the control of zona glomerulosa function.

Aldosterone↗
PubMed1991

Control of steroidogenesis by the calcium messenger system in human adrenocortical cells.

The involvement of the calcium messenger system in the control of steroidogenesis in the rat and bovine adrenal cortex has been studied extensively. However the role of these second messengers in the control of human adrenocortical function is not established. This was therefore studied by incubating collagenase-dispersed human adrenocortical cells with the calcium ionophore A23187 and the protein kinase C activator phorbol 12-myristate 13-acetate (TPA). The effects of the calcium channel blocker verapamil on basal and stimulated steroidogenesis were also studied. Both TPA (1 pmol/l-10 mumol/l) and A23187 (1 nmol/l-10 mumol/l) caused a dose-dependent increase in cortisol, aldosterone and corticosterone production. Verapamil (10 mumol/l) inhibited the increase in aldosterone, corticosterone and cortisol produced in response to ACTH(1-24), potassium, and desacetyl-alpha MSH. Unlike previous results in the rat, these effects were not specific for aldosterone secretion. The results suggest that, as in other species, calcium mobilization and protein kinase C activation have a role in the control of steroidogenesis in the human adrenal cortex. However, in contrast to the rat, these mechanisms appear to be involved in the control of steroidogenesis in both the zona glomerulosa and inner zone cells.

Adrenal Cortex↗
PubMed1991

The role of endothelin in the control of adrenocortical function: stimulation of endothelin release by ACTH and the effects of endothelin-1 and endothelin-3 on steroidogenesis in rat and human adrenocortical cells.

The rate of blood flow through the intact adrenal gland is closely linked to steroid hormone secretion, and although the mechanism involved is unknown, it is thought to involve secretory products of the vascular endothelium. In dispersed cell preparations, endothelin-1 and -3 both caused a dose-dependent and highly sensitive increase in steroid secretion by zona glomerulosa and zona fasciculata cells of the rat and human adrenal cortex. In addition, when the perfused rat adrenal was stimulated with ACTH, significant increases in steroid secretion and perfusion medium flow rate were accompanied by significantly increased secretion of immunoreactive endothelin into the adrenal vein. It is proposed that endothelin has a role in mediating the adrenocortical response to ACTH stimulation.

Adrenal Cortex↗
PubMedDate not supplied

The role of endothelial cell products in the regulation of adrenocortical function: actions of endothelin, nitric oxide, adrenomedullin and PAMP.

There is evidence to suggest that the cells of the vascular endothelium secrete factors, including endothelin-1, nitric oxide, adrenomedullin and PAMP which have a role in regulating adrenal function. There is strong evidence from many studies that each of these factors is able to affect aldosterone secretion, with much less evidence relating to glucocorticoid secretion. The recent evidence suggests that both adrenomedullin and PAMP, like endothelin-1, stimulate aldosterone secretion. The controversies surrounding this issue are discussed. What emerges most strongly from the literature, however, is the evidence that, in addition to being secreted by the vascular endothelium of the adrenal, the peptides endothelin-1 and adrenomedullin are produced within the zona glomerulosa cells themselves, suggesting an autocrine as well as a paracrine role in the regulation of zona glomerulosa function and aldosterone secretion.

Adrenal Cortex↗
PubMedDate not supplied

Internalisation of the type I angiotensin II receptor (AT1) and angiotensin II function in the rat adrenal zona glomerulosa cell.

Using a specific monoclonal antibody (6313/G2) to the first extracellular domain of the type 1 receptor (AT1), we showed that most of the receptor is internalised in the rat glomerulosa cell. When viable glomerulosa cells are incubated with 6313/G2, the receptor is transiently concentrated on the cell surface, and aldosterone output is stimulated. This stimulated output is enhanced by neither threshold nor maximal stimulatory concentrations of AII amide, although the antibody does not inhibit AII binding to the receptor. The antibody directly stimulates inositol trisphosphate (IP3) generation, but, while having no intrinsic action on protein kinase C (PKC) activation, it significantly inhibits the PKC response to angiotensin II. The data suggest that although the receptor is mostly internalized, recycling to the plasma membrane is constitutive, or regulated by unknown factors. Retention of the AT1 receptor in the membrane is alone enough to allow sufficient G protein interaction to generate maximal steroidogenic effects, through IP3 generation. PKC activation induced by angiotensin II has no bearing on steroidogenesis in the dispersed glomerulosa cell system.

Angiotensin II↗
PubMedDate not supplied

Regulation of PAMP and adrenomedullin receptor expression in the rat adrenal zona glomerulosa.

Two peptide hormones are produced from the precursor peptide pre-proadrenoemdullin, known to be expressed in rat zona glomerulosa cells. Receptors for both adrenomedullin and pro-adrenomedullin N-terminal 20 peptide (PAMP) have been identified in the rat adrenal cortex but there is no information to date about the regulation of expression of these receptors, and the significance of these peptides in the regulation of adrenocortical function. In the present study the effects of dietary sodium changes on PAMP and adrenomedullin receptor expression was investigated. Feeding rats a low sodium diet resulted in a decrease in both PAMP and adrenomedullin binding in the zona glomerulosa. Adrenomedullin specific binding was 378 fmol/mg protein in the controls and 89 fmol/mg protein following dietary sodium depletion. PAMP binding was 288 fmol/mg protein in controls and 110 fmol/mg protein in the low sodium group. These data do not support a role for these peptides in the response of the adrenal zona glomerulosa to sodium depletion. It is possible that these peptides may, like ACTH, have acute stimulatory, but long-term inhibitory actions on the zona glomerulosa.

Adrenomedullin↗
PubMedDate not supplied

Adrenomedullin and CGRP receptors mediate different effects in the rat adrenal cortex.

Adrenomedullin (AM) exerts its effects through two distinct receptor subtypes: the AM receptor, and the CGRPI receptor. In most tissues activation of these subtypes brings about similar effects, with only the magnitude of the effect varying. In the rat adrenal cortex, however, this does not appear to be the case. Both CGRPI and AM receptors are present in the rat adrenal cortex. Incubation of zona glomerulosa cells with AM caused an increase in aldosterone secretion, but AM had no effect on angiotensin II-stimulated aldosterone secretion. The action of AM was not affected by CGRP8-37, the CGRP receptor antagonist, suggesting that its effect was mediated by the adrenomedullin receptor. CGRP on the other hand, did not significantly affect basal aldosterone although it attenuated the response to angiotensin II. These data suggest that the CGRP receptor and the AM receptor mediate different effects in the rat adrenal zona glomerulosa.

Adrenomedullin↗