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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of glucocorticoid treatment of DDT1 MF-2 smooth muscle cells on the signaling via two adenosine receptors with opposing actions on cAMP generation was examined. Treatment with dexamethasone caused a dose- and time-dependent increase in the number of adenosine A1 receptors but did not affect the KD or the proportions of receptors in high and low affinity states. The EC50 was 1 nM dexamethasone, and maximal response was achieved after 24 hr. The number of receptors was increased by approximately 50%. Other steroid hormones, including aldosterone, progesterone, testosterone, and estrogen, were much less effective, and addition of the glucocorticoid receptor antagonist RU 486 or the protein synthesis inhibitor cycloheximide prevented the up-regulation, showing that the effect was mediated via a glucocorticoid receptor-specific mechanism that involves protein synthesis. In dexamethasone-treated cells the A1 receptor agonist (-)-N6-phenylisopropyladenosine [(R)-PIA] was 3 times more potent as an inhibitor of cAMP formation induced by isoprenaline than in untreated cells. ADP ribosylation of inhibitory GTP-binding proteins by pertussis toxin completely prevented (R)-PIA from inhibiting cAMP accumulation. A further analysis of the different GTP-binding proteins, including the three Gi subtypes (Gi1, Gi2, and Gi3), revealed no quantitative or qualitative change after dexamethasone treatment. In addition, the adenosine A2 receptors were down-regulated, as indicated by the fact that the ability of the A2 receptor agonist 5'-N-ethylcarboxamidoadenosine to increase cAMP formation was decreased by 20-30% in dexamethasone-treated cells. In summary, we have shown that A1 and A2 receptors on the same cell are differentially regulated by glucocorticoids and that this has functional importance in the regulation of cAMP accumulation.
Mol Pharmacol 1991 Aug
PMID:Glucocorticoid receptor activation leads to up-regulation of adenosine A1 receptors and down-regulation of adenosine A2 responses in DDT1 MF-2 smooth muscle cells. 165 51

We have previously shown that serotonin (5-HT) is a potent stimulator of corticosterone and aldosterone secretion by frog adrenocortical cells and we have demonstrated that the action of 5-HT is not mediated by the classical 5-HT receptor subtypes i.e. 5-HT1, 5-HT2 and 5-HT3. Recently, a non-classical 5-HT receptor (termed 5-HT4) has been characterized using 4-amino-5-chloro-2-methoxy-benzamide derivatives as serotonergic agonists. In the present report, we have investigated the possible involvement of the 5-HT4 receptor subtype in the mechanism of action of 5-HT on steroid secretion. Increasing concentrations of benzamide derivatives (zacopride, cisapride and BRL 24924) gave rise to a dose-related stimulation of corticosteroid production, zacopride being the most potent compound of this series to enhance steroidogenesis. Prolonged administration (230 min) of zacopride induced a rapid increase in corticosterone and aldosterone output followed by a gradual decline of corticosteroid secretion. During prolonged exposure of adrenal tissue to zacopride (10(-5) M), the corticotropic activity of 5-HT (10(-6) M) was totally abolished. The stimulatory effects of 5-HT and zacopride were abolished by the non-selective 5-HT3 antagonist ICS 205 930. In contrast methysergide, a 5-HT1 receptor antagonist, and MDL 72222, a selective 5-HT3 antagonist did not block zacopride-induced corticosteroid secretion. Both 5-HT and zacopride induced a dose-related increase in cAMP production by frog adrenal slices. Taken together, these results indicate that the stimulatory effect of 5-HT on frog adrenocortical tissue is mediated by activation of a 5-HT4 receptor subtype positively coupled to adenylate cyclase.
Brain Res Mol Brain Res 1991 Jun
PMID:Benzamide derivatives provide evidence for the involvement of a 5-HT4 receptor type in the mechanism of action of serotonin in frog adrenocortical cells. 165 92

Angiotensin II (AII) receptor subtypes and their potential coupling mechanisms were studied using recently developed peptide and nonpeptide antagonists in rat and bovine adrenal zona glomerulosa cells, as well as in membranes prepared from rat and bovine adrenal cortex and medulla. Comparison of the potencies of these novel antagonists to displace 125I-[Sar1,Ile8]AII from its binding sites revealed two distinct AII binding sites in membranes prepared from rat adrenal capsules (zona glomerulosa) and from rat adrenal inner zones containing the medulla. About 85% of the binding sites of the glomerulosa zone and 30% of those of the inner zones were of the AT1 subtype, with relative affinities for the nonpeptide antagonists Dup 753 and PD 123177 and the peptide antagonist CGP 42112A in the order of Dup 753 much greater than CGP 42112A greater than PD 123177. In contrast, the relative binding potencies for the other (AT2) population of binding sites were CGP 42112A greater than PD 123177 much greater than Dup 753. Neither AII nor its peptide antagonist [Sar1,Ile8]AII could distinguish between the two sets of binding sites. The effects of the new antagonists on functional responses of rat adrenal glomerulosa cells demonstrated that both AII-stimulated aldosterone production and the AII-induced inhibition of adrenocorticotropic hormone-stimulated cAMP formation were mediated by the AT1 receptor subtype. In bovine adrenals, only AT1 receptors were detected in membranes prepared from the cortex and the medulla, as well as in cultured glomerulosa cells. The relative inhibitory potency of Dup 753 was lower by an order of magnitude at bovine than at rat AT1 receptors. The inhibition of AII-induced aldosterone production by the various antagonists was closely correlated with their inhibitory potencies on 125I-[Sar1,Ile8]AII binding to bovine glomerulosa cells. These data suggest that the known effects of AII in adrenal glomerulosa cells are mediated through the AT1 receptor subtype and that the distribution and/or specificity of the AT2 receptors shows marked species variations.
Mol Pharmacol 1991 Sep
PMID:Angiotensin II receptor subtypes and biological responses in the adrenal cortex and medulla. 165 13

18-Hydroxycortisol has been suggested as a marker compound for a transitional zone between the adrenocortical zonae glomerulosa and fasciculata. The control of secretion of 18-hydroxycortisol has been compared with those of cortisol and aldosterone in normal subjects and patients with primary hyperaldosteronism. Comparisons were also made in isolated bovine zona glomerulosa and zona fasciculata cell preparations. Although there was considerable cross-contamination between fractions, 18-hydroxycortisol secretion occurred with equal facility in both fractions but depended on the availability of cortisol as substrate. Changes in secretion during stimulation following those of cortisol. It is concluded that, in vivo, 18-hydroxycortisol derives mainly from the zona fasciculata. The relevance of these findings to primary hyperaldosteronism and to the nature of the transition is discussed.
J Steroid Biochem Mol Biol 1991 Nov
PMID:The origin and significance of 18-hydroxycortisol: studies in hyperaldosteronism and in bovine adrenocortical cells in vitro. 165 45

In vitro studies on both the purified cytosolic mineralocorticoid receptor (MR) and the recombinant expressed human MR have shown that it is non-specific and does not distinguish between cortisol and aldosterone. These contrast with the apparent in vivo selectivity of the MR in tissues such as the kidney for aldosterone in preference to cortisol despite the 100-fold molar excess of cortisol. This review gives the evidence that indicates that 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD), the enzyme responsible for the interconversion of cortisol and inactive cortisone, acts as a protective mechanism for the MR. In aldosterone-selective tissues it shuttles cortisol to cortisone and thus prevents glucocorticoid access. Aldosterone itself is not a substrate for the enzyme. The current data suggest that this is an autocrine system with both the enzyme and the MR present within the same cell. In certain tissues such as the kidney there may also be additional upstream steroid metabolism indicating a paracrine system. Lack of this protective system results in cortisol acting as a potent mineralocorticoid. This may be congenital as in the apparent mineralocorticoid excess syndrome or acquired secondary to liquorice-induced inhibition of 11 beta-OHSD. In addition to its role in MR protection 11 beta-OHSD may also be important in modulating steroid access to glucocorticoid receptors. The ontogeny of the enzyme in the testis and the brain suggests that its tissue-specific control may be crucial in allowing normal development.
J Steroid Biochem Mol Biol 1991 Nov
PMID:The cortisol-cortisone shuttle and the apparent specificity of glucocorticoid and mineralocorticoid receptors. 165 46

Although we now have a good understanding of some of the mechanisms which control pituitary-adrenal activity in human subjects, there are several important problems which still require a solution. The mechanism which controls the diurnal rhythm of aldosterone secretion is not yet identified, and although ACTH is clearly an important factor in the control of adrenocortical activity, it does not account for the pattern of these changes, or for the changes which occur in adrenal androgen secretion. Corticosteroids are well known to have suppressive effects on the release of ACTH, but the retention of pituitary-adrenal responsiveness in patients receiving ACTH therapy, and the prolonged suppression of the system caused by cortisol-secreting tumours, are not well explained by the model currently used, which needs further refinement.
J Steroid Biochem Mol Biol 1991 Nov
PMID:Adrenal steroid endocrinology--some unsolved problems. 165 47

Pseudohypoaldosteronism is a rare inherited disease characterized by renal salt loss, hyperkalemia and metabolic acidosis despite highly elevated aldosterone values. We previously reported absent or reduced numbers of mineralocorticoid receptors in mononuclear leukocytes and defective effector mechanism as shown by no response in vitro to the incubation of aldosterone in terms of intracellular electrolyte content. We have studied the inheritance of this disorder in ten families and found two different kinds of inheritance: autosomal recessive--often in interrelated families--and autosomal dominant in unrelated families. Parallel studies in the families with the autosomal dominant form of inheritance demonstrated in addition that the effector mechanism of aldosterone is impaired in vitro both in the affected patients and in the carrier relatives characterized by a low number of mineralocorticoid receptors.
J Steroid Biochem Mol Biol 1991
PMID:Pseudohypoaldosteronism and mineralocorticoid receptor abnormalities. 165 76

We elucidated the role of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in human and bovine adrenocortical steroidogenesis. The urinary volume, sodium excretion and cyclic GMP (cGMP) excretion and plasma cGMP were markedly increased by the synthetic alpha-human ANP (alpha-hANP) infusion in healthy volunteers. Plasma arginine vasopressin (AVP) and aldosterone levels were significantly suppressed. Both ANP and BNP inhibited aldosterone, 19-OH-androstenedione, cortisol and DHEA secretion dose-dependently and increased the accumulation of intracellular cGMP in cultured human and bovine adrenal cells. alpha-hANP significantly suppressed P450scc-mRNA in cultured bovine adrenal cells stimulated by ACTH. Autoradiography and affinity labeling of [125I]hANP, and Scatchard plot demonstrated a specific ANP receptor in bovine and human adrenal glands. Purified ANP receptor from bovine adrenal glands identified two distinct types of ANP receptors, one is biologically active, the other is silent. A specific BNP receptor was also identified on the human and bovine adrenocortical cell membranes. The binding sites were displaced by unlabelled ANP as well as BNP. BNP showed an effect possibly via a receptor which may be shared with ANP. The mean basal plasma alpha-hANP level was 25 +/- 5 pg/ml in young men. We confirmed the presence of ANP and BNP in bovine and porcine adrenal medulla. Plasma or medullary ANP or BNP may directly modulate the adrenocortical steroidogenesis. We demonstrated that the lack of inhibitory effect of alpha-hANP on cultured aldosterone-producing adenoma (APA) cells was due to the decrease of ANP-specific receptor, which caused the loss of suppression of aldosterone and an increase in intracellular cGMP.
J Steroid Biochem Mol Biol 1991
PMID:Atrial and brain natriuretic peptide in adrenal steroidogenesis. 165 77

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.
J Steroid Biochem Mol Biol 1991
PMID:Effect of the endothelins on aldosterone secretion by rat zona glomerulosa cells in vitro. 165 81

Pyramidal neurons in the rat CA1 hippocampal area contain both mineralocorticoid (MR) and glucocorticoid receptors (GR) which bind the endogenous adrenal steroid corticosterone with differential affinity. With intracellular electrophysiological recording techniques we have investigated how corticosterone affects the membrane properties of these cells. We observed that low doses (1 nM) of corticosterone or aldosterone can, through MR, reduce the spike frequency accommodation and afterhyperpolarization (AHP) evoked by a short depolarizing current in pyramidal neurons. As the accommodation/AHP can be considered as an intrinsic mechanism of CA1 neurons to attenuate transmission of excitatory input, the MR-mediated action might potentially enhance cellular excitability in the CA1 area. Higher doses of corticosterone or selective glucocorticoids were able to reverse the MR-mediated effect on accommodation/AHP, eventually increasing particularly the amplitude of the AHP. GR-mediated events may thus potentially suppress excitability in the hippocampal CA1 area. Not only current- but also transmitter-induced membrane effects were affected by the steroids. Firstly, GR-ligands were able to suppress a temporary noradrenaline-evoked decrease in accommodation/AHP. Secondly, membrane hyperpolarizations induced by serotonin were reduced by MR-agonists. We propose that cellular excitability in the hippocampus is at least partly under control of coordinative, antagonistic MR- and GR-mediated effects on electrical activity.
J Steroid Biochem Mol Biol 1991
PMID:Effect of corticosteroid hormones on electrical activity in rat hippocampus. 165 84


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