Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031511 (pheochromocytoma)
 14,622 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PC12 cells, derived from a rat pheochromocytoma, were mutagenized and selected in media containing agents known to elevate intracellular concentrations of cyclic AMP (cAMP). More than 40 clones were isolated by selection with cholera toxin or 2-chloroadenosine or both. The variants that were deficient in accumulating cAMP were obtained by using a protocol in which 1 microM 8-bromo-cAMP was included in addition to the agonist. Certain of these variants were partially characterized with respect to the site of altered cAMP metabolism. The profiles of adenylate cyclase activity responsiveness of certain variants to guanosine-5'-(beta, gamma-imido) triphosphate and to forskolin resembled those of UNC and cyc phenotypes of S49 lymphoma cells, which are functionally deficient in the GTP-sensitive coupling protein, Ns. Other variants were characterized by increased cyclic nucleotide phosphodiesterase activity at low substrate concentration. Diverse morphological traits were observed among the variants, but it was not possible to assign them to a particular cAMP phenotype. Two revertants of a PC12 mutant were isolated and observed to have regained a cellular cAMP response to 2-chloroadenosine and to forskolin. It is hoped that these PC12 mutants will have utility for defining cAMP-mediated functions, including any links to the action of nerve growth factor, in cells derived from the neural crest.
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PMID:Mutants of PC12 cells with altered cyclic AMP responses. 609 39

Most beta-adrenergic effects are mediated by activation of the enzyme adenylate cyclase. Hormone binds to the receptor leading to an accelarated binding of GTP to the coupling protein, the N-protein, which is activated. This causes an activation of the adenylate cyclase and an increased formation of cAMP, the intracellular second messenger. The same principles hold good for other hormones coupled to adenylate cyclase. The sensitivity of the adenylate cyclase may be altered in different clinical and experimental conditions. An increased sensitivity is seen in hyperthyroidism in man and in the rat, and during starvation in rats. A decreased sensitivity is seen in hypothyroidism, in patients with pheochromocytoma, pseudohypoparathyroidism type I or multiple symmetric lipomatosis. Several reasons for the altered sensitivity have been suggested. The number of hormone receptors, the coupling between receptor and N-protein, the amount or function of the N-protein or the PDE activity may all vary in different conditions.
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PMID:Coupling between the beta-adrenergic receptor and the adenylate cyclase--pathophysiological implications. 631 52

Tetrahydrobiopterin content was determined in several clonal cell lines by reversed-phase HPLC and subsequent electrochemical detection. The same chromatography system was used to determine the total biopterin (tetrahydrobiopterin and 7,8-dihydrobiopterin) by fluorescence detection. The catecholamine-producing clones neuroblastoma N1E-115 and pheochromocytoma PC-12 contained 96 and 60 ng tetrahydrobiopterin/mg protein, respectively. The corresponding amount for the neuroblastoma clone N2A was 36 ng/mg protein. The tetrahydrobiopterin content in C-6 glioma cells was below the limit of detection. The total biopterin is about 20% above the tetrahydrobiopterin content. Tetrahydrobiopterin and biopterin from the cells were identified by coelution with standard solutions and by potential-current relationship or emission and excitation spectra, respectively. Addition of 2,4-diamino-6-hydroxypyrimidine, an inhibitor of biopterin synthesis from GTP, to the culture medium of PC-12 cells resulted in a dose-dependent decrease of tetrahydrobiopterin and total biopterin content within 4 h, suggesting that the cells are capable of synthesising the biopterin which was found. A decrease in intracellular tetrahydrobiopterin levels by different concentrations of 2,4-diamino-6-hydroxypyrimidine reduces the cellular production of dihydroxyphenylalanine after inhibition of aromatic L-amino acid decarboxylase, indicating that the concentration of tetrahydrobiopterin might be a limiting factor for catecholamine synthesis in catecholamine-producing cells.
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PMID:Tetrahydrobiopterin and total biopterin content of neuroblastoma (N1E-115, N2A) and pheochromocytoma (PC-12) clones and the dependence of catecholamine synthesis on tetrahydrobiopterin concentration in PC-12 cells. 669 75

Complementary DNAs for angiotensin II type 1 receptor isoforms AT1A and AT1B were cloned by expression cloning from bovine adrenal and rat vascular smooth muscles. Human AT1 receptor was also cloned. Seven transmembrane structures emerged. The AT1 type receptor interacted with more than one type of G-proteins. The ligand binding site of AT1 involving Arg167, Lys199, and Asp263 has been identified by site directed mutagenesis. The regulation of the receptors occur at many stages. The isoform, AT2, was also expression cloned from rat pheochromocytoma cells. Although its ligand binding is not affected by stable GTP analogs, it is a seven transmembrane domain receptor. It mediates the modulations of phosphotyrosine phosphatase by angiotensin II and AT2 specific CGP42112A. The modulation was abolished by pertussis toxin. Thus, AT2 belongs to a new class of angiotensin receptors with unique signalling and regulatory mechanisms. AT1 mediates cellular growth. Interestingly, AT2 expression is inversely related to the mitogenic activity of cells.
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PMID:Cloning, expression and regulation of angiotensin II receptors. 748 33

Effects of adenosine on inward current activated by extracellular ATP were examined in rat pheochromocytoma PC12 cells. Adenosine induced two types of modulation on the current activated by 30 microM ATP; a low concentration of adenosine (1 microM) inhibited the current whereas a high concentration (> 10 microM) enhanced the current. Neither the inhibition nor the enhancement was observed in cells pretreated with pertussis toxin (PTX), or in cells dialyzed with guanosine 5'-O-(2-thiotriphosphate) trilithium salt (GDP beta S). In contrast, dialysis with K-252a, a protein kinase inhibitor, abolished the inhibition, but not the enhancement. Adenosine induced similar inhibition and enhancement on ATP-evoked increase in intracellular free Ca2+ concentration. The results suggest that adenosine produces dual modulation on the ATP-activated channels through different mechanisms involving PTX-sensitive GTP-binding proteins.
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PMID:Dual modulation by adenosine of ATP-activated channels through GTP-binding proteins in rat pheochromocytoma PC12 cells. 752 18

We reported earlier that inhibition of adenylyl cyclase activity is a mechanism involved in desensitization of the A2a adenosine receptor-mediated cAMP response (A2a desensitization) in rat pheochromocytoma PC-12 cells. Here, we investigated the molecular mechanism that modulates adenylyl cyclase activity during A2a desensitization. Reversible inhibition of forskolin-evoked adenylyl cyclase activity in desensitized cells occurred after incubation with an A2a-selective adenosine agonist (CGS21680). However, when okadaic acid (a relatively protein phosphatase 2A-specific phosphatase inhibitor) was added after agonist removal, adenylyl cyclase activity did not recover. Okadaic acid caused significant dose-dependent inhibition of adenylyl cyclase activity in intact PC-12 cells. Prolonged exposure of okadaic acid-treated PC-12 cells to adenosine agonists did not evoke further inhibition, suggesting that the inhibition of adenylyl cyclase activity during A2a desensitization may operate through a pathway that overlaps with the increased phosphorylation caused by okadaic acid. Inclusion of calcium in the adenylyl cyclase assay significantly inhibited cyclase activity. indicating that PC-12 cells contain Ca(2+)-inhibitable type VI adenylyl cyclase (AC6). This was confirmed by polymerase chain reaction-based detection of AC6 cDNA. Furthermore, incubation of PC-12 cell membrane fractions with purified protein phosphatase 2A or coexpression of protein phosphatase 2A with AC6 in COS-1 cells significantly increased AC6 activity. To reduce the possible influence of Gs alpha protein, we substituted guanosine-5'-O-(2-thio)diphosphate and MnCl2 for GTP and MgCl2, respectively, in some cyclase assays and found that the suppression of AC6 during A2a desensitization and okadaic acid treatment remained largely unchanged. Taken together, these data suggest that phosphorylation of AC6 might account for the inhibition of adenylyl cyclase activity during A2a desensitization in PC-12 cells.
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PMID:Regulation of adenylyl cyclase type VI activity during desensitization of the A2a adenosine receptor-mediated cyclic AMP response: role for protein phosphatase 2A. 762 63

Mechanisms underlying facilitation by dopamine of extracellular adenosine 5'-triphosphate (ATP)-activated current were investigated in rat pheochromocytoma PC12 cells using the whole-cell voltage-clamp techniques. Dopamine (10 and 100 microM) augmented the peak amplitude of an inward current elicited by ATP (3-100 microM). The activation time course of the ATP-evoked current was accelerated by dopamine; the presence of 10 microM dopamine shifted the dependence of activation rate constants on the concentration of ATP toward a lower concentration range two fold. Dopamine also accelerated the inactivation and the deactivation, which was determined from the current decay upon washout of ATP. Intracellular mediators responsible for the dopamine-induced facilitation was estimated by loading various compounds in patch pipettes. Facilitation was not observed when K-252a (1 microM), a protein kinase inhibitor, was included in the intracellular solution. In addition, facilitation was also attenuated by intracellular adenosine 5'-O-(thiotriphosphate)tetralithium salt (ATP gamma S (1 mM) or alpha-beta-methylene ATP (1 mM). Inclusion of adenosine 3',5'-cyclic monophosphate sodium salt (cAMP, 100 microM), guanosine 3',5'-cyclic monophosphate sodium salt (cGMP, 100 microM), 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 microM) or phorbol-12,13-dibutyrate (1 microM) in the intracellular solution did not affect the facilitation. Guanosine 5'-O-(thiotriphosphate)tetralithium salt (GTP gamma S, 500 microM) or guanosine 5'-O(2-thiodiphosphate)-trilithium salt (GDP beta S, 500 microM) did not modify the facilitation either.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms underlying facilitation by dopamine of ATP-activated currents in rat pheochromocytoma cells. 768 86

cDNA clones encoding the low molecular weight GTP-binding proteins ral A (951 bp) and ral B (2073 bp), including the entire coding region (618 bp), were isolated from a rat PC12 pheochromocytoma library. Northern analyses demonstrated that both ral A and ral B are widely expressed in rat tissues. Two ral A transcripts of 1.1 and 2.9 kb were observed in most tissues in varying proportions. The 1.1 kb ral A band of testes was further shown to be composed of two closely migrating species. In contrast to these findings, a single ral B transcript of 2.3 kb was detected in most tissues. Steady-state levels of ral A transcripts appear greater than ral B. Quantitatively, the testes exhibited the highest ral A and ral B mRNA levels, with lower levels observed in the brain, adrenal and pituitary glands, kidney and ovary. Ral mRNA levels were lowest in muscle tissue, particularly skeletal muscle.
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PMID:Isolation of cDNA clones and tissue expression of rat ral A and ral B GTP-binding proteins. 768 39

Angiotensin II isoform 1 (AT1) receptor cDNAs were cloned by expression cloning from bovine adrenal and rat vascular smooth muscles. Human AT1 receptor was also cloned. Seven transmembrane structures emerged. A single type of receptor seems to interact with more than one type of G-protein. AT1 consists of subtypes AT1A and AT1B, and the regulation of the receptors occurs at many stages. The isoform AT2 was also expression cloned from rat pheochromocytoma cells. Although its ligand binding is not affected by GTP analogs, it is a seven transmembrane domain receptor. It mediates the inhibition of phosphotyrosine phosphatase by angiotensin II and AT2 specific CGP42112A; the inhibition was abolished by pertussis toxin. Thus, AT2 belongs to a new class of angiotensin receptors with unique signalling and regulatory mechanisms.
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PMID:Cloning, expression and regulation of angiotensin II receptors. 771 98

1. The amphiphilic peptide mastoparan is known to affect phosphoinositide breakdown, calcium influx, and exocytosis of hormones and neurotransmitters and to stimulate the GTPase activity of guanine nucleotide-binding regulatory proteins. Another amphiphilic peptide, adenoregulin was recently identified based on stimulation of agonist binding to A1-adenosine receptors. 2. A comparison of the effects of mastoparan and adenoregulin reveals that these peptides share many properties. Both stimulate binding of agonists to receptors and binding of GTP gamma S to G proteins in brain membranes. The enhanced guanyl nucleotide exchange may be responsible for the complete conversion of receptors to a high-affinity state, complexed with guanyl nucleotide-free G proteins. 3. Both peptides increase phosphoinositide breakdown in NIH 3T3 fibroblasts. Pertussis toxin partially inhibits the phosphoinositide breakdown elicited by mastoparan but has no effect on the response to adenoregulin. N-Ethylmaleimide inhibits the response to both peptides. 4. In permeabilized 3T3 cells, both adenoregulin and mastoparan inhibit GTP gamma S-stimulated phosphoinositide breakdown. Mastoparan slightly increases basal cyclic AMP levels in cultured cells, followed at higher concentrations by an inhibition, while adenoregulin has minimal effects. 5. Both peptides increase calcium influx in cultured cells and release of norepinephrine in pheochromocytoma PC12 cells. The calcium influx elicited by the peptides in 3T3 cells is not markedly altered by N-ethylmaleimide. 6. Multiple sites of action appear likely to underlie the effects of mastoparan/adenoregulin on receptors, G proteins, phospholipase C, and calcium.
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PMID:Effects of the amphiphilic peptides mastoparan and adenoregulin on receptor binding, G proteins, phosphoinositide breakdown, cyclic AMP generation, and calcium influx. 784 73


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