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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human adrenocortical H295R cells express AII receptors which are predominantly of the AT1 but not AT2 subclass. These receptors are functionally coupled to phosphoinositidase C in a manner similar to that seen in fetal human, sheep and bovine adrenocortical cells. Treatment of H295R cells with forskolin or dbcAMP to activate the protein kinase A pathway caused a rapid (maximal by 3 h) and sustained decrease in AT1-R mRNA levels which in turn preceded a time-dependent (maximal by 12 h) and dose-dependent loss of [125I]AII binding and phosphoinositidase C activation on subsequent AII challenge. Thus, both decreased AT1-R mRNA levels and functional receptor expression appear to parallel each other in response to activation of protein kinase A. Activation of the Ca2+/protein kinase C pathways by treatment with AII also caused a rapid (maximal by 3 h) and dose-dependent loss in AT1-R mRNA, but mRNA levels subsequently rose again, approaching control levels by 36 h. Treatment with AII for 48 h had little effect on either [125I]AII binding or the subsequent phosphoinositidase C response. The effect of AII, but not forskolin, was blocked by the presence of cycloheximide. The action of AII on AT1-R mRNA was probably mediated through both protein kinase C and Ca(2+)-sensitive protein kinases as the effect at 4 h was not completely reproduced by phorbol ester alone, but was fully reproduced by a combination of phorbol ester and Ca2+ ionophore. However, increased Ca2+ influx alone, due to treatment with BAYK8644 or elevated extracellular K+, also resulted in a decrease in AT1-R mRNA levels. Thus in the H295R cell, control of AT1-R expression appears to be complex, being achieved at least in part through control of the level of AT1-R mRNA by multiple independent signaling pathways including protein kinase A, protein kinase C and Ca2+.
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PMID:Hormonal regulation of angiotensin II type 1 receptor expression and AT1-R mRNA levels in human adrenocortical cells. 758 78

We have previously shown that the human adrenocortical H295R cell line expresses the type 1 angiotensin II receptor (AT1-R) and that expression of this receptor is downregulated at the level of mRNA by forskolin or dibutyryl-cAMP as well as by angiotensin II (Ang II). In this study we examine the effects of K+ on both AT1-R mRNA and receptors, as monitored through 125I-Ang II binding in the presence of PD 123319. After treatment with a maximal stimulatory steroidogenic dose of K+ (14 mmol/L), H295R cells showed an increase in cytosolic free Ca2+ from 113 to 212 nmol/L. Unlike the effects of Ang II, this increase could be abolished by pretreatment with the Ca2+ channel antagonist nifedipine (1 mumol/L). AT1-R mRNA levels also fell in response to elevated extracellular K+ in a dose-dependent (Kd, 9 mmol/L; maximal fall in message at 12 mmol/L) and time-dependent (maximum 50% at 12 hours) manner. The change in AT1-R mRNA level was less rapid than that in response to activation of phosphoinositidase C by Ang II or adenylyl cyclase by forskolin or by dibutyryl-cAMP. Unlike the action of Ang II but similar to the action of forskolin or dibutyryl-cAMP, the action of K+ was sustained. Changes in mRNA level in response to treatment with K+, Ang II, or dibutyryl-cAMP were also paralleled by changes in 125I-Ang II binding in each case.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potassium negatively regulates angiotensin II type 1 receptor expression in human adrenocortical H295R cells. 776 52

While known to be a potent activator of phosphoinositidase C, angiotensin II (A-II) also causes a small but significant increase in cAMP production through the type 1 A-II (AT1) receptor in bovine adrenocortical cells (Mol Cell Endocrinol 81:33-41, 1991). We have carried out studies on primary cultures of fetal bovine adrenocortical cells to examine the effects of A-II on the expression of cytochrome P450 17 alpha-hydroxylase (P450c17), which is known to be regulated in a cAMP-dependent fashion. Prolonged treatment (48 h) of cells with A-II (10(-7) M) did not give rise to a detectable increase in P450c17 as measured by immunoblotting, although both A-II and the protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA) attenuated the large increase in P450c17 induced by ACTH (10(-8) M). A-II alone (10(-7) M) however, caused a time-dependent increase in cAMP secretion, reaching 8-fold within 3 h. Prolonged treatment of cells with A-II also resulted in a 3-fold increase in P450c17 mRNA within 12 h (10(-7) M), and a dose-dependent increase in 17 alpha-hydroxylase activity within 48 h (16.4-fold max at 10(-7) M). The stimulatory actions of A-II alone (10(-7) M) on cAMP levels, P450c17 mRNA, and 17 alpha-hydroxylase activity were much smaller than in response to ACTH (10(-8) M), but were largely reproduced by TPA (10(-7) M), suggesting a role for protein kinase C in mediating these responses to A-II. These findings indirectly support the hypothesis that A-II alone can stimulate an increase in cAMP in adrenocortical cells. Such a stimulation of cAMP may then result in increased expression of steroidogenic enzymes, as we have shown is the case for P450c17 expression. However, A-II in the presence of ACTH appears to attenuate the ACTH-stimulated expression of P450c17.
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PMID:Angiotensin-II stimulates an increase in cAMP and expression of 17 alpha-hydroxylase cytochrome P450 in fetal bovine adrenocortical cells. 838 Oct 79

Primary cultures of bovine adrenocortical zona fasciculata/reticularis (zfr) cells responded to angiotensin II (AII) with a dose-dependent increase in [3H]thymidine incorporation into DNA. The effect was maximal at 100 nmol/liter AII, and was dose dependently inhibited by (sar1, ala8)-AII (saralasin) and DuP753, but not by PD123177. Both AII-stimulated cortisol secretion and phosphoinositidase C activity were also inhibited by saralasin and DuP753, but not by PD123177. Pharmacological analysis of the antagonism of AII-stimulated cortisol secretion by saralasin and DuP753 produced pA2 values of 8.79 and 7.02, respectively. Whereas the pA2 for saralasin agreed closely with previous measurements in other systems, DuP753 was at least one order of magnitude less potent in inhibiting the action of AII in bovine zfr cells compared to previous measurements in rabbit vascular smooth muscle. We conclude that the steroidogenic and mitogenic effects of AII in bovine zfr cells are mediated by the AT1 receptor.
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PMID:Angiotensin II stimulates growth and steroidogenesis in zona fasciculata/reticularis cells from bovine adrenal cortex via the AT1 receptor subtype. 838 14

Previous studies in ovine adrenocortical cells in vitro have shown angiotensin II (AII) receptors are expressed on the zona fasciculata (ZF) cells and are functionally coupled to phosphoinositidase C and increased [Ca2+]i, but AII stimulation does not cause an acute change in cortisol biosynthesis. AII can, however, chronically regulate differential expression of P450c17 and 3 beta HSD in ovine adrenocortical cells in vitro. We have stained ovine adrenal sections with specific antisera to the angiotensin II Type-1 receptor (AT1-R), as well as P450c17 and 3 beta HSD in order to further test the hypothesis that changes in AT1-R expression underlie changes in zonal expression of P450c17 and 3 beta HSD in vivo. AT1-R expression was found to be highest in the outermost layer of cells (zona glomerulosa, ZG) which stained negatively for P450c17 and only faintly positive for 3 beta HSD, as expected. The adjacent layer of cells (ZF) stained much less strongly for AT1-R but stronger for P450c17 and 3 beta HSD. These findings are consistent with our previously reported in vitro expression data, and suggest that the transition from ZG to ZF phenotype, i.e. increased P450c17 and 3 beta HSD expression, may require reduced expression of AT1-R, but maintenance of reduced levels of AT1-R expression in the ovine ZF still allows for differential control of the P450c17: 3 beta HSD ratio. Thus, even though there is no acute cortisol response to AII alone in these cells, AII stimulation can oppose C19 steroid production in the face of cortisol biosynthesis by the ZF in response to agonists such as ACTH.
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PMID:Immunohistochemical analysis of AT1 receptor versus P450c17 and 3 beta HSD expression in ovine adrenals. 896 82