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

The intracellular mechanisms of action of alpha-MSH in rat adrenocortical cells were examined. When rat adrenal capsule (largely glomerulosa) cells were stimulated with a range of concentrations of alpha-MSH there was significant stimulation of aldosterone secretion at 10(-10) mol/l, although cyclic AMP was not increased until high concentrations of alpha-MSH were used (10(-6) mol/l and above). However, cells incubated with ACTH showed an increase in aldosterone secretion at 10(-11) mol/l and levels of cyclic AMP were elevated at 10(-9) mol ACTH/l. When rat adrenal whole capsules were incubated with alpha-MSH, membrane-bound protein kinase C (PKC) activity was increased and cytosolic enzyme activity decreased, showing PKC activation. Stimulation with angiotensin II also induced translocation of PKC activity, but ACTH did not. When [3H]inositol-loaded glomerulosa cells were stimulated with alpha-MSH there was significant generation of [3H]inositol trisphosphate (IP3) at concentrations of alpha-MSH which stimulated secretion of aldosterone. Significantly increased levels of [3H]IP3 were also measured when loaded cells were exposed to angiotensin II. ACTH did not cause any significant stimulation of [3H]IP3 production at any concentration used. These results indicate that activation of PKC and phospholipase C is important in modulating the steroidogenic effect of alpha-MSH.
 ...
PMID:Studies on the intracellular mechanism of action of alpha-melanocyte-stimulating hormone on rat adrenal zona glomerulosa. 132 51

In Pseudomonas aeruginosa, the effect of different cations on the acid phosphatase activity was studied in order to acquire more information related to a previously proposed mechanism, involving the coordinated action of this enzyme with phospholipase C. Although the natural substrate of this enzyme is phosphorylcholine, in order to avoid the possible interaction of its positive charge and those of the different cations with the enzyme molecule, the artificial substrate p-nitrophenylphosphate was utilized. Kinetic studies of the activation of acid phosphatase (phosphorylcholine phosphatase) mediated by divalent cations Mg2+, Zn2+ and Cu2+ revealed that all these ions bind to the enzyme in a compulsory order (ordered bireactant system). The Km values obtained for p-NPP in the presence of Mg2+, Zn2+ and Cu2+ were 1.4 mM, 1.0 mM and 3.5 mM, respectively. The KA values for the same ions were 1.25 mM, 0.05 mM and 0.03 mM, respectively. The Vmax obtained in the presence of Cu2+ was about twofold higher than that obtained in the presence of Mg2+ or Zn2+. The inhibition observed with Al3+ seems to be a multi-site inhibition. The K'app and n values, from the Hill plot, were about 0.25 mM and 4.0 mM, respectively, which were independent of the metal ion utilized as activator. It is proposed that the acid phosphatase may exert its action under physiological conditions, depending on the availability of either one of these metal ions.
 ...
PMID:Pseudomonas aeruginosa acid phosphatase. Activation by divalent cations and inhibition by aluminium ion. 154 81

Previous studies have demonstrated that TRH is a potent stimulator of alpha-MSH secretion from frog pituitary melanotrophs. In order to determine the intracellular events responsible for TRH-evoked alpha-MSH release, we have investigated the effect of TRH on polyphosphoinositide breakdown in frog pars intermedia. Neurointermediate lobes were labelled to isotopic equilibrium with myo-[3H]inositol. TRH stimulated the rate of incorporation of [3H]inositol into the phospholipid fraction. The effect of TRH was concentration-dependent; half-maximal stimulation of alpha-MSH release and inositol incorporation occurred at 12 and 28 nmol TRH/l respectively. In prelabelled neurointermediate lobes, lithium (10 mmol/l) enhanced the radioactivity in inositol monophosphate, bisphosphate (IP2) and trisphosphate (IP3). LiCl (10 mmol/l) induced a 38% inhibition of alpha-MSH release from perifused neurointermediate lobes but did not impair TRH-induced alpha-MSH secretion. In the presence of LiCl, TRH (1 mumol/l) induced a transient increase of the radioactivity in IP3, which was evident by 30 s and maximal by 1 min (+100%). TRH treatment also increased the radioactivity in IP2, which reached a plateau after 5 min (+100%). The increase in radioactivity in IP3 induced by TRH was closely paralleled by a rapid loss of [3H]phosphatidylinositol bisphosphate (PIP2), which was maximal by 1 min (-70%). These results indicate that, in frog pars intermedia, TRH-evoked alpha-MSH secretion is coupled to breakdown of PIP2. The data suggest that, in amphibian melanotrophs, as previously shown in GH3 tumour cells and in rat pituitary mammotrophs, TRH causes rapid stimulation of polyphosphoinositide-hydrolysing phospholipase C.
 ...
PMID:Thyrotrophin-releasing hormone stimulates polyphosphoinositide metabolism in the frog neurointermediate lobe. 217 40

The action of thyrotropin-releasing hormone (TRH) on melanotrope cells maintained in primary culture was studied with biochemical and electrophysiological techniques. TRH effects on polyphosphoinositide (PPI) breakdown was measured in [3H]myoinositol labelled cells maintained in suspension for 24 hours or in primary culture. TRH (50 nM) or its potent analogue (3Me-His2)-TRH increased total PPI levels by 50-125% in separate experiments after 30 min of treatment whereas corticotropin-releasing hormone (CRF) was without effect. The effect of TRH was dose-dependent (ED50 = 5 nM), the maximal effect being reached with 50 nM TRH. Using the patch-clamp technique in the cell-attached configuration spikes were recorded extracellularly. In 6 of the 13 cells tested, (3Me-His2)-TRH (10 nM) elicited an increase in the spontaneous spiking rate. Furthermore, TRH (50 nM) increased melanocyte-stimulating hormone (alpha-MSH) secretion 2-fold after 8 h of treatment. These results suggested that TRH activated phospholipase C and electrical activity in melanotrope cells; the resulting phosphoinositide breakdown and increase in intracellular free Ca2+ ultimately led to a stimulation of hormone release.
 ...
PMID:Thyrotropin-releasing hormone stimulates porcine melanotrope cells in primary culture. 254 Apr 65

The effect of arginine vasopressin (AVP) and corticotropin releasing factor (CRF) an adrenocorticotropin (ACTH) secretion, phosphatidylinositol breakdown and cAMP accumulation was examined in primary cultures of mouse anterior pituitary cells. AVP and CRF added alone stimulated ACTH secretion in a dose-dependent manner. At 10(-8) M concentration of peptide, AVP and CRF stimulated ACTH secretion 2.8- and 4.6-fold, respectively. AVP and CRF added in combination at equal doses gave an additive effect. CRF enhanced cAMP accumulation, but AVP had no effect on basal or CRF-induced cAMP accumulation. Both forskolin (10(-5) M) and 8-bromo-cAMP (10(-3) M) increased ACTH secretion in these cells by 2.8- and 1.7-fold, respectively. AVP induced the breakdown of phosphoinositides, and CRF alone, or in combination with AVP did not modify this effect. Phorbol 12-myristate 13-acetate (10(-7) M), dioctanoylglycerol (10(-4) M) and phospholipase C (100 mU/ml) also stimulated ACTH secretion in these cells by 4.2-, 2.4-, and 3.7-fold, respectively. Depletion of intracellular and extracellular Ca2+ decreased ACTH secretion, but had no significant effect on CRF-induced cAMP accumulation. However, AVP-induced phosphoinositide breakdown was dependent on extracellular Ca2+. These results indicate that CRF stimulates ACTH secretion via the cAMP-dependent pathway and AVP via the phosphoinositide breakdown-phospholipase C pathway. In the presence of AVP and CRF, both pathways appear to operate independently to produce an additive effect on ACTH secretion.
 ...
PMID:Transmembrane signals mediating adrenocorticotropin release from mouse anterior pituitary cells. 255 Feb 96

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.
 ...
PMID:Cholera-toxin and corticotropin modulation of inositol phosphate accumulation induced by vasopressin and angiotensin II in rat glomerulosa cells. 284 33

Results on the effects of peptides on the phospholipid metabolism and steroid and cyclic AMP (cAMP) outputs of rat adrenal capsular cells (96% zona glomerulosa, 4% zona fasciculata) were obtained in a series of three batch experiments. Their significance was examined by analysis of variance. Incorporation of [32P] into phosphatidylcholine, phosphatidic acid and phosphatidylinositol was measured. Production of [3H]inositol-1 monophosphate, inositol-1,4 bisphosphate and inositol-1,4,5 tris-phosphate was estimated after prelabelling with [3H]inositol followed by 1 min incubation with a steroidogenic stimulus. Angiotensin II (0.25 nmol/l to 0.25 mumol/l) highly significantly (P less than 0.01) stimulated aldosterone and corticosterone outputs, [32P] incorporation into phosphatidic acid and phosphatidylinositol (but not into phosphatidylcholine) and the production of the three [3H]inositol phosphates. Aldosterone and corticosterone outputs were stimulated by alpha-MSH (above 0.1 nmol/l). However, incorporation of [32P] was not significantly increased until 10 mumol alpha-MSH/l but, unlike with angiotensin II, incorporation into phosphatidylcholine was also then stimulated. Also, the production of the inositol phosphates was not increased significantly (P greater than 0.05) by any dose of alpha-MSH (10 nmol/l, 1 mumol/l and 0.1 mmol/l) used. Therefore, it can be concluded that alpha-MSH does not stimulate phospholipase C in rat zona glomerulosa cells. In further experiments, it was also found that there were significant increases in cAMP as well as in steroid outputs above 1 nmol alpha MSH/l (highly significant above 10 nmol alpha-MSH/l). There were plateaux of the outputs of both steroids and cAMP from 0.1 to 1 mumol alpha-MSH/l. However, there were further increases in steroid and cAMP outputs of the capsular cells at higher doses. Concomitant results on the stimulation of corticosterone output by zona fasciculata-reticularis cells indicate that this additional increase was mostly due to the stimulation of the contaminating zona fasciculata cells. It was also confirmed that alpha-MSH preferentially stimulates steroidogenesis by the zona glomerulosa. However, under our conditions, alpha-MSH highly significantly increased the output of cAMP by both zona fasciculata and glomerulosa cells.
 ...
PMID:Effects of alpha-melanocyte-stimulating hormone on the cyclic AMP and phospholipid metabolism of rat adrenocortical cells. 302 Jan 42

Interactions among lithium, calcium, and phorbol esters in the regulation of adrenocorticotropin hormone (ACTH) release were examined in a tumor cell line (AtT-20) of the anterior pituitary. Lithium, which blocks the phosphatase that converts inositol phosphates (IPs) to inositol, increases the levels of IPs in these cells and stimulates ACTH release. This ion potentiates the ability of calcium, an activator of phospholipase C, to raise levels of IPs in these cells and to stimulate ACTH secretion. Pretreatment of AtT-20 cells with calcium specifically abolishes the ACTH release response to lithium or calcium, a result suggesting that these secretagogues may act through a common mechanism to induce hormone secretion. Prior exposure of AtT-20 cells to either lithium or calcium also attenuates the ACTH release induced by phorbol ester, an activator of protein kinase C. To examine the link among lithium, calcium, phosphatidylinositol (PI) turnover, and phorbol ester-evoked ACTH secretion, AtT-20 cells were treated with 1-oleoyl-2-acetoyl-sn-3-glycerol (OAG), an analogue of the diacylgylcerols that are formed by phospholipase C during PI metabolism and that also activate protein kinase C. OAG itself does not alter ACTH release or the levels of IPs in AtT-20 cells. Pretreatment of AtT-20 cells with OAG, however, selectively blocks the ACTH release response to lithium, calcium, or phorbol ester. Furthermore, such pretreatment reduced the ability of lithium to increase levels of IPs. The results suggest that one mechanism of action of lithium is to potentiate selectively an action of calcium, possibly the stimulation of phospholipase C activity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interactions among lithium, calcium, diacylglycerides, and phorbol esters in the regulation of adrenocorticotropin hormone release from AtT-20 cells. 303 56

Intracellular Ca2+ (Cai2+) stores contribute significantly to Ca2+ signaling in many types of cells. We studied the role of inositol trisphosphate (InsP3)-sensitive Ca2+ stores, a principal Cai2+ store that presumably is within the endoplasmic reticulum (ER), in cell signaling by examining the effect of thapsigargin (Tg), an ER Ca2+ pump inhibitor that depletes the ER Ca2+ pool, on ACTH secretion. Preincubation for 6-24 h with 2-20 nM Tg had no effect on the resting cytosolic free Ca2+ concentrations ([Cai2+]) but inhibited the ionomycin-stimulated spike-type increase in [Cai2+], which is mediated by InsP3-independent Cai2+ release from the ER, in a dose-dependent (IC50, 4 nM) and time-dependent manner. In ER Cai(2+)-depleted cells, the spike phase (initial 5 min) of the ACTH secretory response to arginine vasopressin (AVP), which is mediated by InsP3-induced Cai2+ release, was also attenuated (IC50, 7.3 nM). However, the spike phase of the ACTH secretory response to AVP was inhibited to a much greater degree than the spike-type response to ionomycin, suggesting that ER Cai2+ stores might have functions other than simply providing Ca2+ for InsP3-stimulated Cai2+ release. Tg pretreatment (IC50, 12 nM) also markedly inhibited the sustained plateau (final 15-min) phase of the ACTH secretory response to AVP, which is mediated by diacylglycerol-induced activation of protein kinase C and subsequent influx of extracellular Ca2+ via L-type voltage-sensitive Ca2+ channels (VSCC), but had no effect on the sustained (full 20 min) response to dioctanoylglycerol that directly activates protein kinase C. Tg had no effect on specific cell binding of [125I]AVP or on specific cell binding of [3H]phorbol 12,13-dibutyrate (except at 20 nM Tg), an index of protein kinase C concentration, or on protein kinase C activity. AVP significantly stimulated inositol trisphosphate accumulation, but pretreatment with Tg completely abolished this effect of AVP, whereas [3H]myoinositol incorporation into membrane-associated inositol lipids and inositol phosphates was unaffected. Thus, Tg-induced depletion of ER Cai2+ stores inhibited both the spike and plateau phases of the ACTH secretory response to AVP, presumably by inhibiting phospholipase C activity and the resulting generation of InsP3 and diacylglycerol. Preincubation with Tg inhibited, in a dose-dependent (IC50, 13 nM) and time-dependent manner, the sustained ACTH secretory response to corticotropin-releasing hormone (CRH) that is mediated by cAMP-induced activation of protein kinase A and Cae2+ influx via L-type VSCC, and the sustained response to forskolin, which directly activates adenylate cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Role of inositol trisphosphate-sensitive calcium stores in the regulation of adrenocorticotropin secretion by perifused rat anterior pituitary cells. 758 88

While there have been several studies on the actions of opioid peptides on adrenocortical steroidogenesis, the results of these studies have failed to resolve the question as to whether these peptides exert a direct action on the adrenal cortex. The present studies were designed to address this question directly, using collagenase-dispersed rat zona glomerulosa and zonae fasciculata/reticularis cells incubated in vitro. The results obtained clearly show that the opioid peptides tested (beta-endorphin, Leu-enkephalin, Met-enkephalin, and its long-acting analogue, DALA) all exerted a significant stimulatory effect on aldosterone secretion by zona glomerulosa cells and all, except Leu-enkephalin, stimulated corticosterone secretion by inner zone cells. The response was shown to be inhibited by naloxone. There did not appear to be a significant interaction between the effects of ACTH and the opioid peptides on adrenocortical cells. Studies using specific agonists for opioid receptor subtypes (DAMGO, DPDPE and U-50488H, specific for mu, delta and kappa receptors respectively) showed that the effect of opioid peptides on the zona glomerulosa appeared to be mediated exclusively by mu receptors while the response of inner zone cells was mediated by both mu and, to a lesser extent, kappa receptors. Finally, studies on the second messenger systems activated by the opioid peptides and the receptor agonists showed that these peptides act to increase labelling of inositol trisphosphate, and strongly suggest that, in the rat adrenal cortex, both mu and kappa opioid receptors are linked to the activation of phospholipase C.
 ...
PMID:Action of opioid peptides on the rat adrenal cortex: stimulation of steroid secretion through a specific mu opioid receptor. 773 74


1 2 3 4 5 Next >>