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)

In AtT-20 cells somatostatin inhibits the secretion of adrenocorticotropic hormone (ACTH) through the activation of GTP binding proteins (G proteins) linked to second messengers such as calcium and cyclic AMP (cAMP). Recently, it has been proposed that there may be G proteins that regulate directly the exocytotic machinery. We have investigated whether somatostatin could inhibit secretion at a step distal to second messengers through a GTP binding protein. For these studies two experimental paradigms were used: (1) intact cells stimulated by calcium ionophores and (2) digitonin-permeabilized cells exposed to buffers of increasing Ca2+ concentrations. Somatostatin inhibited by 70% the ACTH release caused by the calcium ionophore ionomycin without modifying the ionophore-induced elevation in cytosolic [Ca2+]. This effect was cAMP independent because (1) it was observed in the presence of high concentrations of membrane-permeant cAMP analogues, and (2) it was not accompanied by a change in cAMP levels. The effect was also independent of the levels of activators of protein kinase C because it could be produced in the presence of high concentrations of phorbol esters. The action of somatostatin was prevented by pertussis toxin. In digitonin-permeabilized AtT-20 cells somatostatin inhibited release induced by calcium buffers in a GTP-dependent manner. These two observations indicate the involvement of a G protein. It is proposed that a G protein coupled to somatostatin receptors inhibits the intracellular machinery of secretion at a step distal to second messengers, perhaps at the exocytotic site.
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PMID:Evidence that receptor-linked G protein inhibits exocytosis by a post-second-messenger mechanism in AtT-20 cells. 196 44

During perinatal development, when the size of the Sertoli cell population is determined, Leydig cells produce beta-endorphin, a peptide which may interact with Sertoli cells to modify their FSH-responsiveness, as suggested by our previous work. The goal of the present study was first, to test directly the possibility that beta-endorphin modifies the proliferative response of neonatal Sertoli cells to FSH, and second, to gain information on a mechanism(s) involved in any observed effect. We treated isolated 6-day-old Sertoli cells with FSH or vehicle in vitro and measured their incorporation of exogenous, radiolabeled thymidine with quantitative autoradiography. After 2 days in culture with FSH, we detected a 10-fold increase in the rate of Sertoli cell proliferation. The level of cell division in these FSH-treated cultures was identical to that in other cultures exposed to cAMP under similar conditions. In addition, inclusion of beta-endorphin 3 hr prior to FSH or cAMP decreased the effect of the hormone by 50% but left the cAMP response unchanged. Thus, beta-endorphin acts on isolated, neonatal Sertoli cells at a point prior to intracellular production of cAMP to suppress their response to FSH. When other cultures were treated with pertussis toxin, a blocker of intracellular GTP-binding proteins such as Gi, before sequential addition of endorphin and FSH, the effect of beta-endorphin on FSH-responsiveness was abolished. Moreover, when other cultures were exposed to pertussis toxin in the absence of endorphin, followed by FSH, their response to the hormone was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endorphin suppresses FSH-stimulated proliferation of isolated neonatal Sertoli cells by a pertussis toxin-sensitive mechanism. 213 7

Some of the functional effects of beta-endorphin on immune cells are resistant to inhibition by naloxone. To further characterize the beta-[125I]endorphin-binding site mediating these effects and its response to cations and GTP, the human monocyte-like cell line U937 was used. Incubation of intact cells and beta-[125I]endorphin for 60 min at 4 C demonstrated a saturable, high affinity binding site [Kd = 1.2 +/- 0.5 X 10(-8) M (mean +/- SE; n = 4] competed by equimolar beta-endorphin and N-acetyl (Ac)-beta-endorphin but not by naloxone, morphine, or selective opiate receptor agonists. Competition studies showed that beta-endorphin-(6-31) and beta-endorphin-(28-31) were approximately 5- and 100-fold less potent, respectively, whereas beta-endorphin-(1-16) or -(1-27) was ineffective. Covalent cross-linking of beta-[125I]endorphin to intact cells and resolution by gel electrophoresis showed dominant bands at 59K and 44K and a minor band at 66K. The bands at 44K and 66K were completely displaced by increasing equivalent concentrations of beta-endorphin and N-Ac-beta-endorphin. Increasing concentrations of mono (Na+, K+)- and divalent (Ca2+, Mg2+, Mn2+) cations reduced the binding of beta-[125I]endorphin to U937 membrane; beta-[125I]endorphin binding to rat brain membrane showed similar cation sensitivity. GTP gamma-sulfate (GTP gamma S; 10(-4) M) alone reduced binding to U937 membrane by 25%. In the presence of Na+ (100 or 150 mM) or Mg2+ (10 mM), GTP gamma S reduced binding by an additional 50%. Moreover, GTP gamma S (10(-8)-10(-4) M) in the presence of Na+ (100 mM) reduced binding in a dose-dependent manner, whereas GMP was ineffective. In conclusion, beta-endorphin binds to sites on human U937 cells similar to those observed on normal murine splenocytes. Although naloxone insensitive, these sites exhibit properties, such as size, salt sensitivity, and coupling to a GTP-binding protein, that are similar to those observed for agonist binding to brain opiate receptors.
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PMID:Beta-endorphin binding to naloxone-insensitive sites on a human mononuclear cell line (U937): effects of cations and guanosine triphosphate. 216 44

Na,K-ATPase from duck salt gland and ox brain in the membrane-bound or solubilized form was studied by the radiation inactivation technique using ATP, CTP, GTP or p-NPP as substrates. The values of radiation inactivation size (RIS) were compared with the target size (TS) for the alpha-subunit of the enzyme obtained by an independent method as well as with analytical centrifugation data obtained for C12E8-solubilized enzyme. It was concluded that during ATP (CTP) hydrolysis the enzyme operates as an oligomeric structure; the complex formation requires the presence of K+ and adenosine triphosphate binding to the sites with a low affinity for the nucleotide. Specially designed experiments revealed that the degree of enzyme oligomerization increases with an increase in the microviscosity of the membrane lipid environment.
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PMID:Na,K-ATPase: radiation inactivation studies. 216 88

G protein-mediated effects on cAMP production were evaluated in the corpus striatum of diabetic rats 5 and 14 weeks after alloxan injection by measuring both D1-receptor-induced stimulation and D2-receptor-mediated inhibition of adenylate-cyclase activity. At 5 weeks of diabetes, no obvious alterations of G protein functions were detected. Both dopamine-stimulated adenylate cyclase and bromocriptine-induced inhibition of enzyme activity were indeed similar in control and diabetic animals. Fourteen weeks after alloxan injection, profound alterations were observed. Dopamine-stimulated cAMP production was markedly increased in diabetic rats, whereas bromocriptine ability to reduce cAMP formation was almost abolished at this late stage of diabetes. Hypoactivity of Gi/Go proteins was also confirmed by the reduced ability of the GTP non-hydrolyzable analog GTP-gamma-S to inhibit forskolin-stimulation of adenylate cyclase. These results show an apparent functional imbalance between Gs and Gi/Go-mediated transduction mechanisms, with an increased efficacy of Gs activity likely due to the loss of Gi/Go inhibitory functions. Concomitantly with such transductional alteration detected in chronic diabetes, we observed a marked increase of the striatal content of met-enkephalin, which is known to utilize Gi/Go proteins for inhibition of adenylate cyclase. The measurement of other transmitters (vaso-active intestinal peptide, substance P, serotonin, noradrenaline, and dopamine) did not reveal any difference with respect to controls. The observed transductional defect in diabetic animals and the increased content and/or hyperinnervation by the metenkephalinergic system could be correlated as mutual compensatory mechanisms.
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PMID:Denervation and hyperinnervation in the nervous system of diabetic animals: III. Functional alterations of G proteins in diabetic encephalopathy. 251 14

The signal transducing regulatory protein (Gs alpha) was examined in B16 melanoma clones of low (F1C29) and high (F10C23) experimental metastatic potential. Incorporation of the photoaffinity analogue, [8-azido-gamma-32P]GTP, into Gs alpha was decreased in F10C23 extracts when compared to F1C29. This difference disappeared when the photolabeling reaction was carried out at an elevated temperature which enhanced the rate of GTP exchange, suggesting functional differences in the ability of Gs alpha to bind or release GTP rather than dissimilar intracellular Gs alpha concentrations. Differential Gs alpha photolabeling occurred only during the period of rapid growth when F10C23 cells proliferated faster than F1C29 cells. During the recovery phase of growth immediately following plating and at confluence, periods in which F1C29 and F10C23 growth rates are similar, Gs alpha photolabeling between the two clones was equal. CMT lung carcinoma clones of differential metastatic potential grew at a uniform rate at all stages of growth and also exhibited equal Gs alpha photolabeling. F10C23 cells were more responsive to alpha-melanocyte-stimulating hormone stimulation of adenylate cyclase activity than F1C29 cells at all growth stages. These results confirm previously observed functional differences in Gs alpha between B16 metastatic variants and show that photolabeling differences in Gs alpha are related to growth rate.
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PMID:Growth rate dependence of differential incorporation of a guanosine triphosphate photoaffinity probe into the alpha subunit of a guanine nucleotide binding protein, Gs, from metastatic variants of B16 melanoma cells. 254 98

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

The expression of opioid receptors and GTP-binding proteins was studied in 14 pheochromocytomas. The amounts of [3H]diprenorphine bound to membranes varied from 13 to 62 fmole/mg protein, but significantly higher in adrenaline-secreting tumors than in noradrenaline-secreting tumors. None of [3H]DADLE, [125I]beta-endorphin or [3H]ethylketocyclazocine binding was correlated with [3H]diprenorphine binding. Gpp(NH)p inhibition of [3H]DADLE binding was evident in all four normal human adrenal medullae but in only 8 out of 14 pheochromocytomas. The extent of Gpp(NH)p inhibition was not correlated with the amount of pertussis toxin (PT)-sensitive GTP-binding proteins as measured by PT-catalyzed [32P]ADP-ribosylation. The present findings suggest that opioid receptors and PT-sensitive GTP-binding proteins are variously expressed in transformed chromaffin cells, pheochromocytoma.
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PMID:Varying expression of opioid receptors and GTP-binding proteins in human pheochromocytomas. 282 58

The radiation inactivation analysis of Na+, K+-ATPase, (EC 3.6.1.37) from two different sources was carried out using ATP, CTP, GTP and p-NPP as substrates. In the case of Na+, K+-ATPase from the bovine brain the relation between the logarithm of the residual activity and the radiation dose is strictly linear, which permits calculating 75-90 kDa (for 3 mM GTP and 10 mM p-NPP). Duck salt glands Na+, K+-ATPase reveals larger target sizes: 350 kDa for ATP hydrolysis in saturating concentrations and 145-190 kDa in the case of GTP and p-NPP or low concentration of ATP (30 microM). A conclusion is drawn that while hydrolyzing substrates with complex kinetics (ATP and CTP) the enzyme functions like oligomer. The interaction of nucleotide with substrate-binding site of low affinity induces the aggregation of monomers.
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PMID:[Study of the interaction of Na+,K+-ATPase protomers using the molecular target method]. 283 45

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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