Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Y1 adrenal tumor cells are resistant to the steroidogenic effect of A-II though they possess specific A-II binding sites. The number of these binding sites is lower in Y1 cells than in bovine adrenal cells, but the affinity is similar in the two models. Moreover, Y1 cells are shown to contain a high level of cytosolic protein kinase C whose properties appear similar to those observed in bovine adrenal cells. However, the activation of protein kinase C by a phorbol ester (PMA) or diacylglycerol (OAG) does not induce steroidogenesis in Y1 cells. On the other hand, A-II, without any effect on adenylate cyclase in basal conditions, reduces the ACTH-induced cAMP production in Y1 cells. This inhibitory effect of A-II is not blocked by phosphodiesterase inhibitor but is completely abolished after 24 hours of pretreatment of intact cells with pertussis toxin. This inhibition is probably mediated by the inhibitory guanine nucleotide regulatory protein (Gi) since the labeled 41 KD-ADP ribosylated protein disappeared after 24 hours of pretreatment of intact cells with pertussis toxin. Moreover, the accumulation of inositol phosphates under A-II stimulation was low, which suggests that the coupling of A-II receptors with phospholipase C is reduced in Y1 cells. The Y1 cell line is probably a good model to study the post membrane events in A-II action.
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PMID:Angiotensin II (A-II) steroidogenic refractoriness in Y-1 cells in the presence of A-II receptors negatively coupled to adenylate cyclase. 282 18

Using freshly isolated bovine adrenal glomerulosa cells we examined the inhibitory effect of atrial natriuretic peptide (ANP) on aldosterone secretion stimulated by agonists that use either the Ca2+-phosphoinositide or cAMP messenger system. In a continuous perifusion system, angiotensin II (AII) induces a prompt initial rise in aldosterone secretion, followed by a sustained secretory response. Both phases of secretion are rapidly and independently inhibited by ANP. The role of two cyclic nucleotides, cGMP and cAMP, as mediators of this ANP-induced inhibition was examined. The effect of 8-bromo-cGMP (1-100 microM) or (Bu)2cGMP (1-50 microM) on the AII-stimulated rate of secretion was studied in a perifusion system. Either analog, whether added early or late, maximally inhibited by 20-30% only the late or sustained phase of aldosterone secretion. The effect of ANP on cellular cAMP content was examined in a static incubation system. Although ANP caused a reduction in the cAMP content of cells stimulated with either AII or ACTH, it had little or no effect on the cAMP levels in cells stimulated with carbachol. In AII- and ACTH-stimulated cells, the relationship between reduced cAMP content and reduced secretion was explored. In the AII-stimulated cell inhibited by ANP, simple restoration of cAMP content with forskolin did not restore the secretory rate. Pertussis toxin treatment blocked the inhibitory effect of ANP on cAMP content, but did not block its inhibition of secretion. In the ACTH-stimulated cell, reversal of the ANP-induced reduction of cAMP with forskolin, partially restored the stimulated rate of secretion, although restoration of cAMP with a 10-fold higher dose of ACTH did not restore the stimulated rate of secretion in the presence of ANP. These results imply that both the ANP-induced rise in cGMP and the ANP-induced decrease in cellular cAMP content may contribute to the inhibition of steroidogenesis. However, these inhibitory messages do not induce either the magnitude or the temporal pattern of inhibition induced by ANP. Thus, in the adrenal multiple messenger systems may underlie the action of ANP.
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PMID:The role of cyclic nucleotides in atrial natriuretic peptide-mediated inhibition of aldosterone secretion. 283 96

The corticotropin (ACTH) or cholera-toxin-induced cAMP production by cultured bovine adrenal cells increased progressively between days 0 and 7 of culture. Angiotensin II (A-II), which inhibited both basal and ACTH-stimulated adenylate cyclase of crude adrenal membranes, had no effect on ACTH-induced or cholera-toxin-induced cAMP production by fresh isolated cells (day 0) but progressively potentiated the stimulatory action of both effectors from day 0----1 to day 7 of culture. In contrast, phorbol ester had a potentiating effect on fresh isolated cells. Pretreatment of cells with pertussis toxin enhanced the potentiating effect of A-II on cells between 0 and 3 days of culture, but not after 7 days. ADP-ribosylation by cholera toxin (ribosylating alpha s proteins) or pertussis toxin (alpha i proteins), of adrenal membranes prepared from fresh isolated or cultured cells revealed an increase in alpha s and a dramatic decrease in alpha i, the ratios alpha i/alpha s on days 0, 3 and 7 of culture were 4, 0.6 and 0.1 respectively. These results indicate that (a) A-II had a double effect on ACTH-induced or cholera-toxin-induced cAMP production: one inhibitory mediated by Gi, the other stimulatory mediated by protein kinase C activation; this could explain the lack of apparent effect of A-II on fresh cells; (b) the progressive decrease of alpha i might be responsible for the appearance of the potentiating effect of A-II whereas the progressive increase of alpha s could explain the enhanced responsiveness to ACTH or cholera toxin of cultured cells.
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PMID:Variations in guanine-binding proteins (Gs, Gi) in cultured bovine adrenal cells. Consequences on the effects of phorbol ester and angiotensin II on adrenocorticotropin-induced and cholera-toxin-induced cAMP production. 283 73

Vasopressin (VP) and angiotensin II (AT II) stimulate the production of inositol phosphates (IP) in rat glomerulosa cells. Guanosine 5'-[gamma-thio]triphosphate (GTP[S]), but not VP or AT II, stimulates IP production in a myo-[3H]inositol-prelabelled glomerulosa-cell membrane preparation. In combination with GTP[S], these hormones potentiate the response to GTP[S], indicating the existence of a G-protein involved in the coupling of the VP and AT II receptor with the phospholipase C. ADP-ribosylation with pertussis toxin (IAP) revealed the specific labelling of a single molecule of 41 kDa. No significant inhibition of VP- or AT II-stimulated IP accumulation was detected in intact cells when the whole 41 kDa molecule was endogenously ADP-ribosylated by IAP treatment. On the contrary, when glomerulosa cells were infected with cholera toxin (CT), both the VP- and AT II-stimulated IP accumulations were inhibited in a dose-dependent manner. Yet these effects were partial even at high concentrations of CT, and could not be related to the ADP-ribosylation of 'alpha s' molecules. Similarly, when the cells were infected with 1 microgram of CT/ml, the specific binding of VP and AT II decreased by 50-60%. Such results may signify that the treatment primarily affects the densities of the hormone receptors. When glomerulosa cells were incubated for 15 h in the presence of 10 nM-corticotropin (ACTH), a condition in which the intracellular concentration of cyclic AMP was increased 3-fold, the maximum IP response to 0.1 microM-VP or -AT II was decreased by 50%. When similar experiments were carried out only after a 15 min incubation period with the same concentration of ACTH, the increase in cyclic AMP was more pronounced, but no inhibition of hormone-induced IP accumulation was observed. Altogether, these results may suggest that CT exerts its action on the VP- or AT II-sensitive phospholipase C systems via a prolonged increase in intracellular cyclic AMP.
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PMID:Cholera-toxin and corticotropin modulation of inositol phosphate accumulation induced by vasopressin and angiotensin II in rat glomerulosa cells. 284 33

Y-1 adrenal cells contain specific vasopressin (VP) binding sites (27,000 +/- 2,000 sites/cell) of high affinity (KD = 2.2 +/- 0.5 X 10(-9) M). VP which alone has no effect on cAMP production inhibited in a dose-dependent manner (ID50 = 3.5 +/- 0.7 X 10(-11) M) the ACTH-induced cAMP production by Y-1 cells. The inhibitory effect was completely blunted by a 24 h pretreatment of cells with 1 microgram/ml of pertussis toxin. Moreover, VP also stimulated in a dose-dependent manner (ED50 = 2.4 +/- 0.8 X 10(-9) M) the accumulation of inositol phosphates indicating that the VP receptors in Y-1 cells were of the V1 subtype. However, neither VP nor a phorbol ester (4 beta-phorbol 12-myristate 13-acetate, PMA) was able to stimulate Y-1 cell steroidogenesis. Since in a previous work we have shown that Y-1 cells contain high levels of protein kinase C, the present results indicate that the steroidogenic refractoriness of these cells to VP and PMA might involve some step beyond protein kinase C.
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PMID:Vasopressin induces breakdown of phosphoinositides in adrenal tumor Y-1 cells without a steroidogenic effect. 285 Feb 47

Somatostatin (SRIF) inhibits stimulated cyclic AMP accumulation and adrenocorticotropin (ACTH) release from mouse anterior pituitary tumor cells (AtT-20/D16-16). In order to determine whether guanine nucleotide inhibitory proteins (Ni) mediate these effects, AtT-20 cells were treated with pertussis toxin, an agent that inactivates Ni. Pertussis toxin catalyses the ADP-ribosylation of a 41,000 MW protein in membranes of AtT-20 cells. Pretreatment with pertussis toxin prevents the subsequent ability of toxin to catalyse the labeling of Ni. This effect is dependent on the time of pretreatment and is not reversible. The inhibition of SRIF of forskolin-stimulated cyclic AMP accumulation and ACTH release is prevented by pertussis toxin treatment. The blockade is dependent on the time and concentration of toxin used and is not reversible. Pertussis toxin treatment prevents SRIF from inhibiting corticotropin releasing factor and cholera toxin-stimulated cyclic AMP synthesis. The inhibition of K+ and 8-bromocyclic AMP-stimulated ACTH release by SRIF is attenuated partially by toxin treatment. The ability of forskolin and cholera toxin to stimulate cyclic AMP formation and ACTH release is enhanced by treatment of AtT-20 cells with pertussis toxin. The increased cyclic AMP response to forskolin is prevented by cycloheximide. The data indicate that Ni mediates the inhibition by SRIF of cyclic AMP formation and the ACTH release that results from adenylate cyclase stimulation.
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PMID:Pertussis toxin treatment blocks the inhibition of somatostatin and increases the stimulation by forskolin of cyclic AMP accumulation and adrenocorticotropin secretion from mouse anterior pituitary tumor cells. 285 41

Somatostatin inhibits agonist-stimulated cAMP synthesis and ACTH secretion from mouse pituitary tumor cells. It also decreases basal hormone release without affecting cAMP levels and inhibits ACTH secretion in response to agonists whose action is independent of prior cAMP synthesis. These inhibitory effects are attenuated by pertussis toxin, suggesting that the inhibitory guanine nucleotide-binding regulatory subunit of adenylate cyclase modulates effectors, other than adenylate cyclase, during transduction of negative hormonal signals.
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PMID:The inhibitory guanine nucleotide-binding regulatory subunit of adenylate cyclase has an adenylate cyclase-independent modulatory effect on ACTH secretion from mouse pituitary tumor cells. 285 6

The release of ACTH from a clonal cell line of the mouse anterior pituitary (AtT-20/D16-16) can be stimulated by forskolin, 8-bromo-cAMP, and K+. SRIF and its structurally related analogs are very potent inhibitors of the ACTH release response to these secretagogues. The potency of SRIF, its analogs, and somatostatin-28 to inhibit stimulated ACTH release is relatively the same for each of these three secretagogues. The mechanisms by which SRIF regulates the secretion of ACTH can be differentiated by various pharmacological manipulations. Pretreatment of AtT-20 cells with SRIF (10(-7) M) desensitizes SRIF's inhibition of forskolin but not K+ or 8-bromo-cAMP-stimulated ACTH release. Pertussis toxin pretreatment abolishes SRIF's inhibition of forskolin-stimulated ACTH release but not SRIF's inhibition of the ACTH release response to K+ or 8-bromo-cAMP. In contrast, increasing the calcium concentration in the medium reduces SRIF's inhibition of K+ but not forskolin or 8-bromo-cAMP-stimulated ACTH release. These results suggest that SRIF regulates ACTH release from AtT-20 cells through multiple mechanisms. If SRIF acts through a single receptor to produce its effects on ACTH release, then the data imply that the SRIF receptor is coupled to more than one second messenger system.
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PMID:Multiple mechanisms of somatostatin inhibition of adrenocorticotropin release from mouse anterior pituitary tumor cells. 285 83

Both forskolin, the activator of adenylate cyclase, and 8-bromocyclic (cAMP) increase cytosolic calcium levels (measured using Quin 2) and adrenocorticotropin (ACTH) release from a tumor cell line of the mouse anterior pituitary (AtT-20/D16-16). Somatostatin (SRIF) blocks the ACTH release response to each secretagogue but only inhibits forskolin-stimulated calcium mobilization suggesting that SRIF prevents the formation of cAMP rather than blocking the ability of cAMP to raise intracellular calcium concentrations. SRIF itself lowers intracellular calcium levels. The ACTH release response but not the rise in cytosolic calcium levels induced by the membrane-depolarizing agent K+, is blocked by SRIF, indicating that SRIF can interfere with some intracellular event, other than calcium mobilization or cAMP formation, to reduce ACTH secretion. Pertussis toxin uncouples SRIF receptors from adenylate cyclase by catalyzing the ADP-ribosylation of an inhibitory guanine nucleotide binding protein (Ni) in AtT-20 cell membranes. Pretreatment of AtT-20 cells with pertussis toxin abolishes the inhibition by SRIF of the ACTH release response and of the rise in cytosolic calcium induced by forskolin. In addition, the ability of SRIF to inhibit basal calcium levels is prevented by pertussis toxin treatment. Pertussis toxin treatment also reduced the ability of SRIF to inhibit K+-evoked ACTH release. SRIF receptor binding studies using the ligand 125I-CGP-23996 revealed that pertussis toxin treatment greatly diminished the affinity of the SRIF receptor for SRIF and its structural analogs. These results indicate that, in addition to coupling SRIF receptors to adenylate cyclase, Ni is also involved in the lowering by SRIF of resting calcium levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pertussis toxin blocks somatostatin inhibition of calcium mobilization and reduces the affinity of somatostatin receptors for agonists. 286 3

The involvement of guanine nucleotide regulatory proteins in the steroidogenic response of the adrenal glomerulosa to angiotensin II (AII) was investigated by analyzing the effects of Bordetella pertussis toxin (PT) on several aspects of AII action. These included receptor binding, stimulation of aldosterone production and GTPase activity, inhibition of cAMP production, and attenuation of the aldosterone response at high angiotensin concentrations. Pretreatment of glomerulosa cells with PT abolished the inhibitory effects of both AII and somatostatin (SRIF) on ACTH-stimulated cAMP production. Under the same incubation conditions, the stimulation of aldosterone secretion by submaximal and maximal steroidogenic concentrations of AII was completely unaffected by the toxin. However, the attenuation of steroid responses seen with supramaximal concentrations of AII was abolished. In addition, the ability of SRIF to inhibit AII-stimulated steroid production was markedly reduced by PT treatment. The binding of [125I]AII to high affinity sites in intact cells and particulate fractions, and modulation of the binding by guanine nucleotides, were unaffected by toxin pretreatment, even under conditions where a 40-41K protein was completely ADP ribosylated. In contrast, the toxin substantially diminished the binding of [125I]Tyr0-SRIF to SRIF receptors in glomerulosa cells (by 50% after 5 h and by 90% after 20 h). These results indicate that Ni or a similar protein probably mediates the inhibition of cAMP formation by AII and the attenuation of the steroid response by high concentrations of AII as well as the inhibitory actions of SRIF in the adrenal glomerulosa cell. Furthermore, the lack of effect of PT on AII binding and stimulation of GTPase activity suggests the existence of an additional pertussis-insensitive guanine nucleotide-regulatory protein that is activated by lower concentrations of AII and mediates the stimulation of aldosterone production.
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PMID:Control of aldosterone production by angiotensin II is mediated by two guanine nucleotide regulatory proteins. 288 77


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