Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatostatin, morphine, and opioids inhibit transmitter release at intact neuromuscular junctions between ciliary ganglion neurons and the choroidal smooth muscle of the chick eye. Somatostatin and morphine, however, have no effect on release from terminals on the striated muscle target of the ciliary ganglion, the iris. In neuronal terminals of both the choroid and the iris, a high-affinity Na+-dependent choline uptake-mediated ACh synthesis is present at hatching. Both tissues exhibit a basal release of 3H-ACh which is potentiated severalfold during a 5 minute incubation in 55 mM K+ Tyrodes. Fifty percent of the basal release and 100% of the stimulated release are Ca2+ dependent and probably mediated through N-like voltage-dependent Ca2+ channels. Co-incubation of the choroid with 10 microM morphine sulfate blocks approximately 90% of the stimulated release. The same effect is seen with 100 nM somatostatin, 10 microM dynorphin, and 100 microM met-enkephalin arginine phenylalanine. Preincubation of the excised choroid with pertussis toxin (200 ng/ml) reverses the inhibitory effects of both morphine and somatostatin. In contrast, 3H-ACh release from terminals in the striated iris is not affected by either morphine or somatostatin at micromolar levels. These results suggest that both opiate and somatostatin receptors are present in the choroid target and that they may act through a final common pathway to modulate ACh release via G proteins. Second messengers such as cyclic AMP or diacylglycerol do not appear to mediate these effects; neither increasing cAMP levels in terminals nor activation of protein kinase C affects evoked release or its inhibition by morphine or other neuromodulators. It is unclear whether endogenous neuromodulation occurs in this system, although somatostatin-like immunoreactivity can be demonstrated in terminals of choroid neurons.
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PMID:Opiate and peptide inhibition of transmitter release in parasympathetic nerve terminals. 256 61

The effects of the alpha-melanocyte-stimulating hormone (alpha-MSH) (10(-7)-10(-5) M) and the beta-adrenoceptor agonist isoprenaline (10(-9)-10(-4) M) on adenylate cyclase (AC) activity were investigated in homogenates of the human IGR 1 melanoma cells with or without additional GTP. Basal AC activity was increased by the administration of 10 microM GTP. Alpha-MSH had no effect on cyclic AMP (cAMP) accumulation, while isoprenaline stimulated AC activity in a dose-dependent manner.
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PMID:Adenylate cyclase activity in homogenates of human melanoma cells. Effect of alpha-MSH and isoprenaline. 256 44

In humans the major stimulus for cutaneous pigmentation is ultraviolet radiation (UVR). Little is known about the mechanism underlying this response, in part because of the complexity of interactions in whole epidermis. Using a recently developed culture system, human melanocytes were exposed daily to a physiologic range of UVR doses from a solar simulator. Responses were determined 24 hours after the last exposure. There was a dose-related increase in melanin content per cell and uptake of 14C-DOPA, accompanied by growth inhibition. Cells from donors of different racial origin gave proportionately similar increases in melanin, although there were approximately tenfold differences in basal values. Light and electron microscopy revealed UVR-stimulated increases in dendricity as well as melanosome number and degree of melanization, analogous to the well-recognized melanocyte changes following sun exposure of intact skin. Similar responses were seen with Cloudman S91 melanoma cells, although this murine cell line required lower UVR dosages and fewer exposures for maximal stimulation. These data establish that UVR is capable of directly stimulating melanogenesis. Because cyclic AMP elevation has been associated in some settings with increased pigment production by cultured melanocytes, preliminary experiments were conducted to see if the effects of UVR were mediated by cAMP. Both alpha-MSH and isobutylmethylxanthine (IBMX), as positive controls, caused a fourfold increase in cAMP level in human melanocytes and/or S91 cells, but following a dose of UVR sufficient to stimulate pigment production there was no change in cAMP level up to 4 hours after exposure. Thus it appears that the UVR-induced melanogenesis is mediated by cAMP-independent mechanisms.
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PMID:Ultraviolet radiation directly induces pigment production by cultured human melanocytes. 282 34

S-100 protein in clonal GA-1 and C6 rat glioma cell lines was released in serum-free medium supplemented with adrenocorticotropic hormone (ACTH). The induction of S-100 protein release by ACTH was dose-dependent, showing a half-maximal release at about 5 microM, and the S-100 protein concentration in the medium increased sharply within 3 min, but slightly during further incubation. The S-100 protein release was apparently accompanied by a decrease in the membrane-bound form of S-100 protein in the cell. The S-100 protein release was induced not by the ACTH1-24 fragment, which exhibits the known effects of ACTH, but by the ACTH18-39 fragment, which is designated as corticotropin-like intermediate-lobe peptide (CLIP). These results indicate that the C-terminal half of ACTH is responsible for the S-100 protein release. The enhancement of S-100 protein release by ACTH was also observed in normal rat glioblasts. The release induced by ACTH was apparently specific to S-100 protein, because little release of the cytoplasmic enzymes, creatine kinase, and enolase was observed under the same conditions. High concentrations (5 mM) of dibutyryl cyclic AMP or dibutyryl cyclic GMP were also found to induce S-100 protein release; however, catecholamines (epinephrine, norepinephrine, isoproterenol, and dopamine), acetylcholine, and glutamic acid did not enhance the release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:S-100 protein in clonal astroglioma cells is released by adrenocorticotropic hormone and corticotropin-like intermediate-lobe peptide. 282 56

Adrenodoxin is an iron-sulfur protein which functions as a carrier of reducing equivalents in steroid hydroxylation reactions catalyzed by specific cytochromes P-450 in steroidogenic tissues such as adrenal cortex. Purified bovine adrenocortical adrenodoxin was shown to be selectively phosphorylated upon incubation with purified cAMP-dependent protein kinase, whereas other protein kinases were ineffective. The phosphorylation reaction was completed within 45 min at 30 degrees C and resulted in the optimal incorporation of 1 mol phosphate/mol adrenodoxin. Apoadrenodoxin, lacking the iron-sulfur cluster, was also phosphorylated under similar conditions. An apparent Km of 55 microM with a Vmax of 0.3 pmol 32P incorporated min-1 mg adrenodoxin-1 was calculated. Phosphorylation resulted in a striking change in several molecular properties of adrenodoxin, such as electrophoretic behavior and hydroxyapatite affinity, thus providing the possibility of clearly separating phosphorylated from unphosphorylated adrenodoxin. In addition, phosphoadrenodoxin became refractory to mild trypsin degradation, whereas this was not the case with apoadrenodoxin. The phosphorylated site of adrenodoxin was identified as a serine residue; study of peptide products resulting from CNBr and proteolytic cleavages of phosphoadrenodoxin suggested that Ser-88 was the target of the phosphorylation reaction. The influence of phosphorylation upon adrenodoxin activity was examined using cholesterol side-chain cleavage and 11 beta-hydroxylase (11 beta) systems, reconstituted from purified components. Phosphorylation of adrenodoxin resulted in an average twofold decrease in its Km values for the two specific cytochromes P-450 involved. This effect was paralleled by a positive relationship between the degree of adrenodoxin phosphorylation and its ability to support the overall activity of reconstituted side-chain cleavage and 11 beta-hydroxylase systems. Although it remains to be examined whether adrenodoxin is phosphorylated in the intact cell, the present observations suggest that it represents a potential target in the hormonal regulation of the adrenocortical differentiated functions, especially by stimulatory agents acting through a cyclic-AMP-dependent mechanism, such as adrenocorticotropin.
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PMID:Phosphorylation of bovine adrenodoxin. Structural study and enzymatic activity. 282 99

Aldosterone secretion from adrenal glomerulosa cells can be stimulated by angiotensin II (AII), extracellular potassium and adrenocorticotropin (ACTH). Since the mitochondria can recognize factors generated by AII (cyclic-AMP-independent) and ACTH (cyclic AMP dependent), it is reasonable to postulate the existence of a common intermediate in spite of a different signal transduction mechanism. We have evaluated this hypothesis by stimulation of mitochondria from glomerulosa gland with fractions isolated from glomerulosa gland stimulated with AII or from fasciculata gland stimulated with ACTH; the same fractions were tested using mitochondria from fasciculata cells. Postmitochondrial fractions (PMTS) obtained after incubation of adrenal zona glomerulosa with or without AII (10(-7) M) or ACTH (10(-10) M), were able to increase net progesterone synthesis 5-fold in mitochondria isolated from non-stimulated rat zona glomerulosa. In addition, AII in zona glomerulosa produced in vitro steroidogenic fractions that were able to stimulate mitochondria from zona fasciculata cells. Inhibitors of arachidonic acid release and metabolism blocked corticosterone production in fasciculata cells stimulated with ACTH. This concept is supported by the experiment in which bromophenacylbromide and nordihydroguaiaretic acid also blocked the formation of an activated PMTS. In fact, non-activated PMTS, in the presence of exogenous arachidonic acid AA, behaved as an activated PMTS from ACTH stimulated cells. We suggest that the mechanisms of action of ACTH and AII involve an increase in the release of AA and an activation of the enzyme system which converts AA in leukotriene products.
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PMID:Leukotrienes as common intermediates in the cyclic AMP dependent and independent pathways in adrenal steroidogenesis. 282 7

The effects of adrenocorticotropic hormone (ACTH), cyclic AMP (cAMP), NADPH, Krebs cycle intermediates (KCl), and metyrapone on the two key mitochondrial reactions in the biosynthesis of glucocorticoids--11 beta-hydroxylation and cholesterol cleavage--were studied in preparations from the adrenal glands of stranded whales (Kogia breviceps and Mesoplodon europaeus) and some terrestrial mammals. ACTH (30 pM) and cAMP (1.0 mM) enhanced the 11 beta-hydroxylation of [11-3H]deoxycorticosterone ([3H]DOC) in monolayer cultures of whale adrenal cells during a 4-hr incubation period. Mitochondria from whale and beef adrenals responded in a similar dose-related fashion to NADPH generated by the addition of increasing amounts of NADP (0-0.6 mM) to the in vitro system: at each level of NADPH, 11 beta-hydroxylation of [14C]DOC was several-fold greater than the cleavage of [14C]cholesterol. Metyrapone interfered in a dose-related manner with both the 11 beta-hydroxylation of [14C]DOC and the cleavage of [14C]cholesterol by mitochondria from whale and beef adrenals; inhibition of 11 beta-hydroxylation exceeded 60% at 0.1 mM metyrapone and was virtually complete at 1.0 mM in both species, while inhibition of [14C]cholesterol cleavage averaged 25% at 0.1 mM metyrapone and 50% at 1.0 mM. The effect of exogenous NADPH in supporting the 11 beta-hydroxylation of [14C]DOC could be maintained in beef and rat adrenal mitochondria to the extent of 70-100% by substitution with any of the KCl. This phenomenon was not found in similar whale studies where the KCl were all ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The adrenal gland of stranded whales (Kogia breviceps and Mesoplodon europaeus): in vitro modulation of mitochondrial steroid enzyme activities. 282 52

Cultured human adrenal cortical adenocarcinoma cells (SW-13) form a confluent monolayer of epithelial-like cells when seeded into culture flasks. Following a 24-48 hr non-mitotic period, cells begin to divide and become confluent within a week after seeding at 5 X 10(4) cells/cm2. The SW-13 cells were exposed to dibutyryl cyclic AMP (DbcAMP), cyclic AMP (cAMP), sodium butyrate, and adrenocorticotropin (ACTH). The rate of SW-13 cell proliferation was measured with a DNA microfluorometric assay, as well as by procedures measuring the incorporation of 3H-thymidine. In addition, following administration of ACTH and DbcAMP, the fractional area of membrane covered by gap junctions was quantitated with freeze-fracture electron microscopic techniques. Dibutyryl cyclic AMP at a concentration of 1 X 10(-3) M decreased the growth rate of the cell population. There was a corresponding increase in the fractional area of gap junctions found on the cell membrane in 96-hr DbcAMP-treated cultures. ACTH (40 mU/ml) exposure failed to produce an increase in the fractional area of gap junctions or to alter the rate of cell proliferation. From these data it can be suggested that elevations in cAMP levels within the cell can be related to both the proliferation of gap junctions and the decrease in cell proliferation in the SW-13 tumor cell.
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PMID:Dibutyryl cyclic AMP modulation of gap junctions in SW-13 human adrenal cortical tumor cells. 283 94

In an attempt to clarify the mechanisms underlying the lack of melanin formation in hair bulb melanocytes of chinchilla mice (genotype a/a, cch/cch, strain PW), we studied the effect of exogenous melanogenic stimulants such as theophylline (Tp), dibutyryl cyclic AMP (db-cAMP), and alpha-melanocyte-stimulating hormone (alpha-MSH) on the induction of melanization. Skin explants excised from the dorsa of chinchilla or lethal yellow C57BL/6J, Ay/a) mice at 7 to 9 days of age were cultured in the presence of Tp (2 mM), db-cAMP (2 mM), or alpha-MSH (1.0 microgram/ml). After 2 to 5 days, melanin formation was induced in hair bulb melanocytes of chinchilla mutant in response to both Tp and db-cAMP, but alpha-MSH did not produce new melanin formation. In contrast, yellow mutant increased the melanin formation in response to all stimulants. Electron microscopic studies demonstrated that while non-treated hair bulb melanocytes of chinchilla mutant contain a large number of stage II-III melanosomes without melanin deposition, a hair bulb treated with Tp exhibits the new formation of melanin within melanosomes that appears both as typical eumelanosomes with striated longitudinal matrices and as pheomelanosomes with vacuolar melanization. Quantitative analysis of melanin has revealed that in chinchilla mutant, Tp and db-cAMP induce a severalfold increase in the formation of both eumelanin [pyrrole-2,3,5-tricarboxylic acid (PTCA)] and pheomelanin (aminohydroxyphenylalanine), whereas alpha-MSH does not stimulate production of either melanin. In yellow mutant, db-cAMP induced a remarkable increase in eumelanin (PTCA), in contrast to the fewfold increase induced by alpha-MSH and Tp. All stimulants induced a slight increase in pheomelanin to a similar extent. These different reactions to melanogenic stimulation suggest a possible defect in the tyrosinase activation system within hair bulb melanocytes in chinchilla mutants.
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PMID:Induction of melanization within hair bulb melanocytes in chinchilla mutant by melanogenic stimulants. 284 Apr 69

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


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