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)

The 1,4-dihydropyridine BAY-K-8644 [methyl-1,4-dihydro-2, 6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5-carboxylate] acts as both a calcium channel agonist and antagonist by stimulating or inhibiting inward calcium current. In AtT-20 mouse pituitary tumor cells, BAY-K-8644 both stimulates and blocks adrenocorticotropin (ACTH) secretion. Because in several cell systems the cytoplasmic enzyme guanylate cyclase is activated, presumably by calcium entry, the effect of BAY-K-8644 on cyclic GMP (cGMP) synthesis in AtT-20 cells was assessed. BAY-K-8644 increased cGMP accumulation in a time-dependent manner. The concentrations of BAY-K-8644, however, required to increase cGMP formation were not associated with its stimulatory effects on secretion but rather with its ability to antagonize basal and (-)-isoproterenol-induced ACTH secretion. The inhibitory effect of BAY-K-8644 on ACTH secretion was not mimicked by 8-Br-cGMP. The cGMP response to BAY-K-8644 was not mimicked by the cationophore, A-23187, or depolarizing concentrations of K+. Other calcium channel antagonists such as nifedipine or verapamil had markedly smaller effects on cGMP formation compared to BAY-K-8644. Sodium nitroprusside and sodium azide both increased cGMP synthesis in AtT-20 cells and both inhibited, to a lesser extent than BAY-K-8644, both basal- and (-)-isoproterenol-stimulated ACTH release. The data suggest that BAY-K-8644 stimulates cGMP synthesis by binding to sites less accessible or poorly activated by other dihydropyridines, and that stimulation of guanylate cyclase is independent of inward calcium current.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:BAY-K-8644-stimulated cyclic GMP synthesis in mouse pituitary tumor cells. 241 44

The present study examines whether a correlation exists between cyclic nucleotides and the mechanism of action of arginine vasopressin (AVP) on adrenocorticotropin hormone (ACTH) secretion from pituitary corticotrophs. Incubation of cultured anterior pituitary cells with 3-isobutyl-1-methylxanthine (IBMX) or Rolipram elevated the basal intracellular content of both adenosine 3':5'-cyclic monophosphate (cAMP) and guanosine 3':5'-cyclic monophosphate (cGMP) or cAMP alone, respectively. Both IBMX and Rolipram enhanced the AVP-stimulated secretion of ACTH in cultured anterior pituitary cells, but not in AtT-20 corticotrophs which lack functional AVP receptors. Rolipram was less potent than IBMX in this regard, which suggests a possible involvement of cGMP. In contrast, both drugs showed similar potency to stimulate CRF-induced ACTH secretion. Incubation of pituitary cells with atrial natriuretic factor elevated tissue cGMP levels and increased the ACTH response to AVP. The results of this study show that, although AVP fails to directly affect the levels of cAMP and cGMP in anterior pituitary cells, the stimulatory effect of AVP on ACTH secretion was modulated by the cellular cAMP content.
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PMID:Indirect relationship between vasopressin-induced secretion of ACTH and cyclic nucleotides in cultured anterior pituitary cells. 246 10

A yin-yang hypothesis is presented linking noradrenergic activity, thromboxane, melatonin, left hemisphere functioning, and cyclic AMP on the one hand, and dopamine, beta-endorphin, calcium, right hemisphere functioning, and cyclic GMP on the other. It is further suggested that there is a yoking of NA, TXA2, serotonin and melatonin in the left hemisphere, and a similar yoking of DA, BE, calcium and cGMP in the right. Evidence is presented to support the hypothesis that each element (NA, TXA2, etc.) on one side can modulate or balance a corresponding element (DA, BE, etc.) on the other. It is suggested that thromboxane is the key element in noradrenergic overactivity and that not taking this into consideration has confounded much prior research. This theory takes into account information processing models as well as pharmacological data and neurochemical theory on coupling of adenylate cyclase to its hormone receptors. Inhibiting noradrenergic overactivity can be obtained by inhibiting thromboxane and concomitantly activating opiate receptors. This protocol may have clinical utility in treating a wide range of disorders such as: anxiety, depression, schizophrenia, sleeplessness, withdrawal states, enuresis, Gilles de la Tourette syndrome, Parkinsonism, Alzheimers, dementia, anorexia, infant ruminations, essential tremor, spasticity of spinal cord injury, diarrhoea, ulcerative colitis, extrapyramidal symptoms, akathisia, neuroleptic malignant syndrome, attention deficit disorder, hyperhidrosis, and possibly AIDS.
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PMID:Inhibiting noradrenergic overactivity by inhibition of thromboxane and concomitant activation of opiate receptors via dietary means. 254 22

In Bomirski Ab amelanotic hamster melanoma cells, L-tyrosine and/or L-dopa induce increases in tyrosinase activity as well as synthesis of melanosomes and melanin. L-tyrosine also modifies melanocyte-stimulating hormone (MSH) binding. In this paper we show that in the Bomirski amelanotic melanoma system MSH and agents that raise intracellular cyclic AMP induce dendrite formation, inhibit cell growth, and cause substantial increases in tyrosinase activity without inducing melanin synthesis. Tyrosinase activity is detected only in broken cell preparations, or cytochemically in fixed cells. In the continued absence of mature melanosomes, the induced enzyme remains in elements of the trans-Golgi reticulum. Comparative measurements of cyclic AMP in amelanotic and tyrosine-induced melanotic cells show similar basal levels. L-tyrosine and L-dopa have little or no effect, whereas MSH may cause a 1000% peak increase in cyclic AMP levels both in amelanotic and melanotic cells. None of these agents influences cyclic GMP or inositol trisphosphate (InsP3) levels. In agreement with the InsP3 assays, phorbol ester (TPA) has no effect on melanization, tyrosinase activity or cell proliferation. In conclusion, in the Bomirski amelanotic melanoma, MSH induces only partial cell differentiation associated with raised levels of cyclic AMP. Induction of melanosome synthesis and melanization by L-tyrosine or L-dopa appear to follow pathways unrelated to cyclic AMP, cyclic GMP or InsP3.
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PMID:MSH inhibits growth in a line of amelanotic hamster melanoma cells and induces increases in cyclic AMP levels and tyrosinase activity without inducing melanogenesis. 255 57

The secretion of corticotropin by perfused rat anterior pituitary cell columns was studied. Forty-one residue corticotropin releasing factor, vasopressin and high extracellular KC1 all stimulated the secretion of corticotropin. The hormonal response to corticotropin-releasing factor (10(-10) mol/l), vasopressin (10(-9) mol/l) as well as KC1 (48 mmol/l) was reduced by membrane permeant analogs of cGMP, such as 8-BrcGMP and dibutyryl-cGMP. The 8-BrcGMP analog (10(-5) mol/l) inhibited corticotropin release in response to corticotropin-releasing factor by 30%, that to vasopressin by 70%, and that to KCl by 50%. Atriopeptin1-28 (10(-8) and 10(-7) mol/l), a peptide known to activate membrane-bound guanylate cyclase in the anterior pituitary gland, decreased the release of corticotropin induced by vasopressin to about 30% of control. Similarly, activators of soluble guanylate cyclase, such as glyceryltrinitrate and sodium nitroprusside (10(-5) mol/l) inhibited vasopressin-stimulated corticotropin release by 60%. In conclusion, the data show that purported activators of particulate and soluble guanylate cyclase, as well as derivatives of cGMP itself are strong inhibitors of secretagogue-induced corticotropin release by corticotroph cells of the anterior pituitary gland.
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PMID:Guanosine 3':5'cyclic monophosphate and activators of guanylate cyclase inhibit secretagogue-induced corticotropin release by rat anterior pituitary cells. 256 41

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

The present study shows for the first time that in proopiomelanocortin cells of the rat intermediate pituitary gland ANF binds to two receptor forms, with apparent molecular weights of 150K and 70K. Scatchard plots revealed specific and high affinity non-interacting sites, with a KD value of about 3 nM and a density of 7,000 sites/cell. The presence of these binding sites was further confirmed by autoradiographic studies. Activation of these receptors led to an increase in cellular content of cGMP, with half-maximal effect being elicited with about 5 nM ANF, while cAMP formation was unaltered. Alpha-MSH secretion of intermediate pituitary cells was unaffected by ANF, whether the cells were incubated in the absence or presence of corticotropin-releasing factor or bromocryptine. These data thus indicate the presence of multiple ANF receptor sites in the intermediate pituitary which are coupled to cell production of cGMP, but independent of alpha-MSH secretion.
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PMID:Binding and effect of atrial natriuretic factor on cyclic GMP formation and alpha-MSH secretion of intermediate pituitary cells. 284 90

The effect of adrenocorticotropic hormone (ACTH) on the intracellular concentration of cyclic nucleotides was studied in cultures of neurons from embryonic chick cerebral hemispheres. Incubation of neurons with ACTH(1-24) in the presence of phosphodiesterase inhibitor isobutylmethylxanthine resulted in a sustained increase in cyclic AMP while rise in cyclic GMP level was transient. The values obtained for half-maximal stimulation were 0.5 microM and 0.03 nM for cyclic AMP and cyclic GMP respectively. Concomitantly, ACTH(1-24) stimulated guanylate cyclase activity (half-maximal stimulation at 0.02 nM). These results suggest the existence of two distinct populations of ACTH receptors in neurons and provide the first evidence that cyclic GMP does mediate the action of ACTH in neurons.
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PMID:Regulation of cyclic AMP and cyclic GMP levels by adrenocorticotropic hormone in cultured neurons. 300 Mar 76

Rats with increased alcohol motivation have been found to have a rise in enkephalin levels in limbic cortex and a decrease in met-enkephalin levels in the brain basal ganglia. Reduction of met-enkephalin to leu-enkephalin ratio in basal ganglia, limbic cortex and hypothalamus may serve as an index of increased inclination to ethanol in these animals. Alcohol dependence is characterized by reduced cAMP content in the majority of brain structures studied, sharply decreased met-enkephalin levels in limbic cortex and hypothalamus, and diminished cAMP and cGMP content in hypothalamus. In the third stage of experimental alcoholism the partial normalization of met-enkephalin and cAMP levels is observed in brain structures, with cGMP content increased in hypothalamus and considerably reduced in basal ganglia.
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PMID:[Enkephalin and cyclic nucleotide content in the brain structures of rats at different stages of the formation and development of alcoholic dependence]. 300 25

Atrial natriuretic factor (ANF) inhibits basal and stimulated aldosterone synthesis in adrenal glomerulosa cells. ANF probably acts through specific membrane receptors. Alterations in cyclic GMP and cyclic AMP levels do not account for ANF's inhibitory effect. ANF does not block angiotensin II (AngII) receptors nor does it interfere with phosphoinositide metabolism or calcium movements stimulated by adrenal agonists. ANF does not inhibit protein synthesis nor does it work by inhibiting NA+,K+-ATPase or depleting cell potassium. ANF decreases conversion of endogenous cholesterol to pregnenolone, the step stimulated by adrenocorticotropin and AngII. ANF does not affect the conversion of 20-alpha-hydroxycholesterol, which easily penetrates mitochondrial membranes to the site of the cholesterol side-chain cleavage enzyme. These results suggest that ANF inhibits the ability of endogenous cholesterol to reach or interact with the side-chain cleavage enzyme. ANF does not act like a calcium channel-blocking agent. However, ANF is less effective at high-calcium concentrations, which suggests that it may inhibit a step that calcium stimulates. Understanding ANF action will probably require identification of the specific biochemical changes (mediators) that it induces. Parallel efforts to understand how other agents stimulate steroidogenesis (particularly in the areas of protein synthesis, protein phosphorylation, and cholesterol movements) will further this understanding.
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PMID:Inhibition of aldosterone synthesis by atrial natriuretic factor. 301 92


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