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)

Phorbol ester (PMA) potentiates ACTH-induced cAMP production by both fresh isolated and 7-day-old cultured adrenal cells, but the effect on cultured cells was greater than in fresh cells. In cultured cells the potentiating effects of PMA were dose-dependent and were observed at each effective dose of ACTH without modification of the ED50 for this hormone. These effects of PMA do not seem to be exerted through a modification of the alpha subunit of Gi since pretreatment of the cells with Bordetella pertussis toxin did not modify the action of PMA and since the amount of alpha i in 7-day-old cultured cells was ten times lower than in fresh cells, while the potentiating effect was lower in the latter. Moreover, since PMA still exerted its potentiating action in cells stimulated by maximal concentration of cholera toxin or forskolin either alone or in combination with ACTH, it is likely that its action is not mediated exclusively by the alpha subunit of Gs. Taken together, the present results and those of the literature suggest that this potentiating effect of phorbol ester on effector-induced cAMP production might be mediated by inhibition of the beta-subunit of G proteins.
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PMID:The potentiating effects of phorbol ester on ACTH-, cholera toxin-, and forskolin-induced cAMP production by cultured bovine adrenal cells is not mediated by the inactivation of alpha subunit of Gi protein. 288 61

Hormonally stimulated secretion of ACTH from AtT-20 mouse pituitary tumor cells is a cyclic AMP-mediated process. The presence of inhibitory cholinergic muscarinic receptors on these cells was recently reported, and in this study, the relationship between the activation of these receptors and the consequent inhibition of cyclic AMP formation and ACTH secretion was investigated. The muscarinic agent, oxotremorine, antagonized both cyclic AMP synthesis and ACTH secretion in response to corticotropin-releasing factor (CRF), vasoactive intestinal peptide, a 27-amino acid peptide with an N-terminal histidine and a C-terminal isoleucine amide, and forskolin. Other muscarinic agents, carbachol and bethanechol, had similar inhibitory effects. The cholinomimetics reduced basal (unstimulated) ACTH secretion without decreasing basal cyclic AMP levels, and also antagonized hormone release in response to cyclic AMP-independent agonists such as K+, A-23187, and phorbol ester. Scopolamine reversed the inhibitory effects of the muscarinic agents on basal and stimulated ACTH secretion and cyclic AMP formation. Increasing the extracellular calcium concentration reversed the muscarinic antagonism of basal and CRF-stimulated hormone release without affecting the cyclic AMP response. Pertussis toxin pretreatment attenuated the inhibitory effects of the muscarinic agents on forskolin-stimulated cyclic AMP synthesis and ACTH secretion as well as the inhibitory effect of carbachol on basal ACTH release. The data suggest that cyclic AMP is an essential mediator in the ACTH secretory pathway, but that an alternate cyclic AMP-independent ACTH pathway also exists in the clonal cells, and that both pathways may be modulated by a common postcholinergic receptor mechanism.
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PMID:Inhibition of ACTH secretion in mouse pituitary tumor cells by activation of muscarinic cholinergic receptors. 299 73

We observed that cepharanthine might exert its anti-allergic action by stimulating the secretion of corticosterone. The present experiments were carried out to investigate stimulation of the pituitary-adrenocortical system by cepharanthine. Administration of cepharanthine to rats produced increases in plasma and adrenal corticosterone levels. Administration of cepharanthine to propranolol pretreated rats also produced increases in plasma and adrenal corticosterone levels and plasma ACTH level. The elevation of corticosterone level induced by cepharanthine was considered to be the specific effect of cepharanthine. Cepharanthine did not increase plasma corticosterone level in rats in the state of dexamethasone suppression of the pituitary-adrenocortical system, in which the level was lowered. Administration of cepharanthine to Bordetella pertussis vaccine induced beta-adrenergic blocked rats also produced increases in plasma and adrenal corticosterone levels. The production and release of corticosterone from an adrenal cell suspension were not influenced by cepharanthine in vitro. These results suggest that cepharanthine stimulates the pituitary-adrenotropic function.
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PMID:[Stimulation of pituitary-adrenocortical system by cepharanthine]. 300 88

Angiotensin II (AII) receptors in adrenal glomerulosa cells are coupled to adenylate cyclase inhibition. We investigated the importance of cyclase inhibition in adrenal steroidogenesis by treating adrenal glomerulosa cells with the toxin of Bordetella pertussis (20 ng/ml) for 3 and 18 h. This treatment prevented inhibition of forskolin-stimulated adenylate cyclase by AII. However, the aldosterone response to AII was not altered by toxin treatment. These results strongly suggest that adenylate cyclase inhibition is not directly involved in mediating the adrenal actions of AII. In addition, ACTH-induced steroidogenesis also was unaffected by toxin treatment demonstrating that cyclase inhibition is not involved in suppressing steroidogenesis via the cAMP pathway.
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PMID:Adenylate cyclase inhibition is not involved in the adrenal steroidogenic response to angiotensin II. 301 40

We have described relationships involving forskolin stimulation of adenylate cyclase (AC) from a variety of sources and the potentiation of forskolin effects by stimulatory hormones (glucagon, ACTH, and epinephrine) and beta, gamma-imidoguanosine 5'-triphosphate (Gpp(NH)p). The effects on AC were examined using membrane preparations of rabbit adipocytes, rat adipocytes, rat erythrocytes, and rat liver. Also examined was the AC of liver membranes of rat pretreated with pertussis toxin as well as that solubilized from rat liver membranes. Maximal forskolin stimulation of AC in all preparations studied revealed a consistent 10-fold increase in AC activity. The EC50 for forskolin was 10 microM for rat liver, 15 microM for rabbit and rat adipocytes and 17 microM for rat erythrocyte AC stimulation. In all cases the AC activity attained by forskolin stimulation was further enhanced by stimulatory hormones in a dose-dependent manner. Furthermore, a combination of all three activators (forskolin, stimulatory hormone, and Gpp(NH)p) resulted in an even greater overall stimulation to levels ranging from 25- to 30-fold over unstimulated activity levels. In the presence of saturating levels of each stimulatory hormone and Gpp(NH)p, the EC50 for forskolin diminished markedly to the range of 0.5 to 4.0 microM. In the absence of any apparent tissue specificity for forskolin stimulation, the general pattern of these results further implicates the catalytic site of the AC complex as the site of forskolin activation. Furthermore, activation of additional components of the complex by Gpp(NH)p and tissue specific hormones may further influence the AC activity and thereby potentiate the stimulation by forskolin.
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PMID:A dose-response study of forskolin, stimulatory hormone, and guanosine triphosphate analog on adenylate cyclase from several sources. 302 68

Exposure of bovine adrenocortical cells to optimal concentrations of angiotensin II (A II) resulted in an almost 2-fold enhancement of cellular cAMP accumulation in response to steroidogenic concentrations of ACTH. This effect was dose-dependent and transient, with a maximum after 4-6 min of treatment with A II. Activators of protein kinase C such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and 1,2-dioctanoyl-sn-glycerol mimicked that effect in a sustained fashion. The ACTH-sensitized state of the adrenocortical adenylate cyclase system induced by TPA exhibited also an enhanced response to forskolin. On the other hand, previous treatment of the cells by pertussis toxin suppressed any further effect of TPA. It is suggested that, following A II exposure, the Gi inhibitory components of the adrenocortical cell adenylate cyclase system may be inactivated, leading to increased response to ACTH. This process may involve protein kinase C activation, subsequent to intracellular generation of lipidic messengers resulting from accelerated phosphoinositide breakdown induced by angiotensin.
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PMID:Sensitization of adrenocortical cell adenylate cyclase activity to ACTH by angiotensin II and activators of protein kinase C. 303 95

Pertussis toxin was purified approx. 1800-fold from pertussis vaccine. Administration of as little as 1 microgram of toxin/100 g body weight to hamsters markedly decreased the sensitivity of their adipocytes to agents that inhibit adenylate cyclase through receptor-mediated, GTP-dependent mechanisms such as alpha 2-adrenergic amines, prostaglandins, phenylisopropyladenosine and nicotinic acid. On the contrary, the inhibitory effect of 2',5'-dideoxyadenosine on cyclic AMP accumulation was not affected by the toxin. Activation of adenylate cyclase by isoproterenol, ACTH or forskolin was not diminished by the toxin but the maximum cyclic AMP accumulation was consistently increased. Furthermore, the dose-response curves for ACTH and forskolin were clearly shifted to the left in adipocytes from toxin-treated hamsters as compared to control adipocytes. It is concluded that pertussis toxin blocks the transfer of inhibitory information from the receptors to adenylate cyclase.
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PMID:Effect of pertussis toxin on the hormonal regulation of cyclic AMP levels in hamster fat cells. 631 62

We used the PCR amplification technique in an attempt to characterize further the dopamine D2L receptor expressed in the prolactin-secreting pituitary MMQ cell clone, derived from the prolactin- and ACTH-secreting Buffalo rat 7315 alpha pituitary tumour. By semiquantitative PCR amplification we were unable to detect the mRNA encoding the D2S receptor isoform, which derives from the well-known process of alternative splicing, producing two D2 receptor subtypes (D2L and D2S) in such tissues as the anterior pituitary and the corpus striatum. Although the pharmacology of the D2 receptor has been established in many studies on both native receptors and transfected receptor isoforms, because of the lack of tissues naturally expressing only one receptor isoform, MMQ cells represent the first example of cells uniquely or prevalently expressing only the D2L receptor, conceivably coupled to its native transduction mechanisms. These considerations prompted us to evaluate the pharmacology and the second messenger systems known to be modulated by dopamine. Scatchard analysis of [3H]spiperone binding resulted in a linear plot, consistent with the existence of a single class of binding sites, with a Kd of 0.055 +/- 0.002 nM and a Bmax of 27 +/- 3.5 fmol/mg protein. Competition experiments confirmed the GTP-dependence and the order of potency for agonist and antagonist ligands consistent with binding to a D2 receptor. The inhibitory effects of dopamine on adenylyl cyclase activity, inositol phosphate production and intracellular free calcium concentrations, the latter presumably via the opening of K+ channels, and prolactin secretion, as well as the reversal of the effect by the D2-selective antagonist (-)sulpiride and pretreatment with pertussis toxin, are consistent with the known biological actions of dopamine at D2 receptors. Based on our observations, the MMQ cell line can be considered a useful tool for investigating ligand-receptor interactions to develop new selective dopaminergic D2L ligands for the therapy of dopamine-related disorders such as schizophrenia, depression, Parkinson's disease and drug addiction.
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PMID:Absence of D2S dopamine receptor in the prolactin-secreting MMQ pituitary clone: characterization of a wild D2L receptor coupled to native transduction mechanisms. 766 27

Angiotensin-II (AII), which stimulates steroidogenesis in bovine adrenocortical (BAC) cells through the phosphoinositides pathway, activates p42-p44 mitogen-activated protein kinases (MAPKs) after 5 min of treatment (EC50 = 0.1 nM). This activation is 1) completely inhibited by the AII receptor AT1 subtype antagonist Dup 753 (10 microM), but unaffected by the AT2 antagonist PD 123177; 2) not reproduced by the AT2 agonist CGP 42112A; 3) insensitive to pretreatment with pertussis toxin; and 4) abolished by a 48-h preexposure of the cells to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA; 1 microM), which down-regulates protein kinase-C activity. Fibroblast growth factor-2, a potent mitogen for BAC cells, which acts through its tyrosine kinase receptor, also activates MAPK (EC50 = 0.3 in a TPA-insensitive manner, while exhibiting no detectable effect on BAC cell steroidogenesis. In contrast, ACTH, which stimulates steroidogenesis via cAMP and inhibits BAC cell proliferation, does not stimulate MAPK. Indeed, ACTH completely blocks (IC50 = 0.01 nM) the stimulation of MAPK by AII, fibroblast growth factor-2, or TPA. Therefore, bovine adrenocortical cells provide an example of positive and negative hormonal regulation of MAPK activity through a cross-talk between the inositide-, cAMP-, and growth factor-activated tyrosine kinase pathways.
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PMID:Hormonal regulation of mitogen-activated protein kinase activity in bovine adrenocortical cells: cross-talk between phosphoinositides, adenosine 3',5'-monophosphate, and tyrosine kinase receptor pathways. 786 5

It is well known that cholera toxin (CT) stimulates ADP-ribosylation of Gs and also pertussis toxin (PT) does Gi. Each GTP-binding protein has its own action in the regulation of adenylate cyclase. A human non-functioning adrenocortical cancer tissue showed an unresponsiveness in adenylate cyclase to ACTH although ACTH and CT activated adenylate cyclase in a non-functioning adrenal adenoma tissue. CT ADP-ribosylated 43 kDa protein of the plasma membrane of the cancer tissue while CT and PT could ADP-ribosylate 43 kDa and 38 kDa protein in the adenoma tissue, respectively. Immunoblotting analysis of the cancer tissue demonstrated that 40 kDa protein was detected by anti-Gs antibody as well as by anti-Gi antibody. The present experiments demonstrated that CT could ADP-ribosylate Gs which has stimulatory action on adenylate cyclase and also Gi which inhibits adenylate cyclase. Thus it is suggested that CT can activate the ADP-ribosylation of Gs and also Gi in a human adrenocortical cancer tissue, partly resulting in abnormal regulation of adenylate cyclase which may be crossly related to ACTH-unresponsiveness.
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PMID:Cholera toxin can ADP-ribosylate Gs as well as Gi in ACTH-unresponsive human adrenocortical cancer. 788 22


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