Biomedical subjects

X B Wang

Publications and source records attributed to X B Wang.

At least 73 records · Page 4Linked to original sources

PubMed1991

Dual effect of osmotic cell swelling on prolactin secretion by acutely dispersed adenohypophyseal cells.

Cell swelling induced by acute exposure to the permeant molecule urea or by medium hyposmolarity evoked a prompt PRL secretory burst from dispersed rat anterior pituitary cells. However, during continuous exposure greater than or equal to 10 min to these conditions inhibition of basal and TRH-induced PRL secretion occurred and there was an "off" burst of PRL secretion following return to basal conditions. Compared with continuous TRH stimulation which causes biphasic PRL secretion with a rapid high amplitude first phase secretory burst followed by a sustained low level second phase of secretion, cell swelling induced only "first phase" secretion. Removing Ca2+ from the medium or adding 50 microM verapamil markedly depressed the "off" secretory burst following return to basal conditions but had no effect on the initial high amplitude burst. Our data suggest that the effect of cell swelling on PRL secretion is complex and that there are at least two mechanisms for PRL secretion in normal anterior pituitary cells; these are differently affected by cell swelling and Ca2+ influx.

Animals↗

PubMed1991

Dopamine inhibits cell swelling-induced prolactin secretion in MMQ cells by blocking Ca2+ influx.

To evaluate the role of Ca2+ influx on hormone secretion induced by cell swelling, we have utilized a prolactin (PRL)-secreting rat tumor cell line, MMQ, which has plasmalemma dopamine receptors. Medium hyposmolarity or osmotically equivalent isotonic urea caused prompt cell swelling and a rise in both [Ca2+]i and PRL secretion in a dose-dependent manner. Dopamine inhibited the induced increase in both [Ca2+]i and PRL secretion in a dose-dependent manner but the maximum inhibition was only 50%. This effect of dopamine was prevented by haloperidol. Depletion of medium Ca2+ or blocking Ca2+ influx with nifedipine completely abolished the osmotically induced rise in both [Ca2+]i and PRL secretion. These data indicate that Ca2+ influx through nifedipine-sensitive Ca2+ channels is an essential component of PRL secretion induced by osmotic cell swelling in MMQ cells and that a dopaminergic receptor-linked mechanism influences the opening of these channels.

Animals↗

PubMed1991

Hormone secretion stimulated by ethanol-induced cell swelling in normal rat adenohypophysial cells.

Ethanol has been reported to affect endocrine functions, but its mechanism of action is unclear. To evaluate the hypothesis that cell swelling induced by ethanol permeation through the plasmalemma triggers hormone secretion, we studied the effect of ethanol on both hormone secretion and cell volume in acutely dispersed rat adenohypophysial cells under isotonic and hypertonic conditions. Isotonic ethanol caused a prompt cell swelling and an explosive secretory burst of prolactin and thyrotropin, which were proportional to the concentration of ethanol between 10 and 120 mM. The lowest effective dose of isotonic ethanol was 10 mM, which is below the plasma levels of legal intoxication (16 mM). Removal of medium Ca2+ enhanced the isotonic ethanol-induced increases in both cell volume and secretion. Hypertonic ethanol was ineffective in these effects. These data indicate that, in normal rat adenohypophysial cells, cell swelling caused by the rapid passage of ethanol through the plasmalemma is a potent mechanism for stimulating hormone secretion and this induced secretion is negatively modulated by extracellular Ca2+.

Animals↗

PubMed1991

The contrasting role of calcium influx in secretion induced by cell swelling can differentiate normal and tumor-derived rat pituitary cells.

We have evaluated whether cell swelling may be a generally useful technique to differentiate normal and neoplastic pituitary cells, making the comparison between normal lactotrophs and thyrotrophs and tumor-derived GH4C1 and MMQ cells. With 1.5 mM medium Ca2+, cell swelling induced by osmotically equivalent stimuli, 27% medium hyposmolarity or 80 mM isotonic urea, caused a prompt increase in both intracellular Ca2+ and hormone secretion by all cell types. Depletion of medium Ca2+ abolished the cell swelling-induced increase in intracellular Ca2+ in all cell types and hormone secretion in the tumor-derived cells. However, it enhanced hormone secretion in normal cells. The critical role of Ca2+ influx in osmotically induced secretion in neoplastic, but not normal, pituitary cells may reflect some fundamental alteration in the intracellular transduction system in tumor cells.

Animals↗

PubMed1991

Significant qualitative differences exist between thyrotropin and prolactin secretory dynamics induced by pituitary cell swelling.

Cell swelling produced by a variety of techniques is a potent stimulus intensity-related inducer of an immediate secretory burst of thyroid-stimulating hormone (TSH) and prolaction (PRL) secretion from anterior pituitary cells. A 2-min "square wave" exposure to either hyposmolarity or isotonic urea induced stimulus intensity-correlated TSH and PRL secretory bursts peaking within 3 min, but the PRL zenith occurred 1 min later than that of TSH. With continuous exposure to these stimuli, TSH secretion rapidly decreased and remained only slightly above the unstimulated rate after 5 min. PRL secretion fell to and remained below the unstimulated level after 10 min. After stopping the stimulus, another secretory burst ("off" response) occurred with PRL, but not with TSH. A progressive "ramp" increase in stimulus intensity over 18 min induced a corresponding gradual increase in TSH secretion; there was a progressive depression, rather than increase, in PRL secretion during the stimulus ramp, with an off response secretory burst when the stimulus was discontinued. Removal of extracellular Ca2+ or addition of verapamil to the medium did not alter the dynamics of hyposmolarity-induced TSH secretion, but markedly altered those of PRL secretion; there was no off response PRL secretion and a hyposmolar ramp induced a corresponding gradual increase in PRL secretion, with a return to baseline after removing the stimulus. The dramatic qualitative differences in the response of the thyrotroph and lactotroph may reflect differences between the cell types in the size of secretory vesicles, membrane potential, the mechanism of exocytosis, and/or the role of Ca2+ influx across the plasmalemma.

Animals↗

PubMed1991

Quinidine inhibits prolactin secretion induced by thyrotropin-releasing hormone, high medium potassium or hyposmolarity in GH4C1 cells.

In cultured GH4C1 cells quinidine inhibited basal prolactin (PRL) secretion and that induced by 0.1 to 10 nM thyrotropin-releasing hormone (TRH), 30 mM medium K+ or 30% medium hyposmolarity but did not inhibit secretion induced by 100 nM 12-O-tetradecanoylphorbol 13-acetate. Inhibition of basal PRL secretion was highly correlated with the drug concentration between 30 microM to 1 mM quinidine; 50% inhibition of basal secretion occurred at 300 microM and at this concentration quinidine completely blocked PRL secretion stimulated by TRH, K+ and hyposmolarity. Significant inhibition of TRH-induced PRL secretion was produced by 15 microM quinidine, a concentration equivalent to that in plasma during standard antiarrhythmic therapy with quinidine in humans. In rats in vivo, a single injection of 2 mg i.p. of quinidine gluconate/100 g b.wt. 1 hr before TRH injection significantly inhibited induced TSH secretion by 15%. Quinidine inhibition of secretion may be caused by blocking depolarization of the cell membrane, thus depressing voltage-gated Ca++ channels and preventing a rise in intracellular Ca++ release.

Anti-Arrhythmia Agents↗

PubMed1990

Lidocaine and procaine inhibit the increase in cytosol Ca2+ induced by thyrotropin-releasing hormone or K+ depolarization in GH4C1 cells.

Lidocaine at greater than or equal to 1 mM and procaine at greater than or equal to 2.5 mM exerted dose-dependent inhibition of the increment in [Ca2+]i induced by 100 nM thyrotropin-releasing hormone (TRH) or 30 mM K+ in GH4C1 cells. The rise in [Ca2+]i induced by K+ was more sensitive to this inhibition than that induced by TRH. Lidocaine was more potent than procaine in inhibiting the [Ca2+]i increment induced by secretagogues. Maximal lidocaine inhibition of the TRH-induced [Ca2+]i increment occurred within 15-20 min and a normal response to secretagogues returned within 20 min after removal of lidocaine from the incubation medium. Our data suggest that in GH4C1 cells local anesthetics depress secretagogue-induced intracellular Ca2+ mobilization, depolarization of the cell membrane, and the opening of voltage-dependent Ca2+ channels. This may explain the depression of secretagogue-stimulated hormone secretion induced by these agents.

Animals↗

PubMed1990

The rate of increase not the amplitude of cytosolic Ca2+ regulates the degree of prolactin secretion induced by depolarizing K+ or hyposmolarity in GH4C1 cells.

Depolarizing K+ and medium hyposmolarity caused striking rises in both cytosolic free Ca2+ concentration [( Ca2+]i) and prolactin (PRL) secretion in GH4C1 cells, which were completely blocked by removal of medium Ca2+. However, the increase in [Ca2+]i and PRL secretion induced by hyposmolarity was clearly slower than that induced by K+. Although there was a good correlation between the zenith of PRL secretion and [Ca2+]i induced by various intensities of K+ or hyposmolarity, the regression slopes were significantly different between the K(+)-and hyposmolarity-induced changes (P less than 0.01). There was a good correlation between the maximum rate of change in PRL secretion and that of the increase in [Ca2+]i when the data from the 2 secretagogues were combined (r = 0.994, P less than 0.001, N = 9). We suggest that the rate of increase in [Ca2+]i may be more important than the amplitude of [Ca2+]i in stimulating PRL secretion.

Animals↗

PubMed1990

The permeant molecule urea stimulates prolactin secretion in GH4C1 cells by inducing Ca2+ influx through dihydropyridine-sensitive Ca2+ channels.

Isotonic urea in medium with a normal 1.2 mM Ca2+ concentration induced a striking rise in both cytosolic Ca2+ concentration ([Ca2+]i) and prolactin (PRL) secretion, each of whose peaks were proportional to the concentration of urea between 5 and 120 mM. There was a significant linear relationship between the peaks of induced [Ca2+]i and PRL secretion (r = 0.99, P less than 0.001). The increase in both [Ca2+]i and PRL secretion was completely abolished by removal of medium Ca2+ or by 2 microM nifedipine. Hypertonic urea was ineffective in inducing either an increase in [Ca2+]i or PRL secretion. These data support the hypothesis that plasma membrane expansion is a potent non-toxic inducer of hormone secretion and that in GH4C1 cells an increase in [Ca2+]i produced by enhanced influx of extracellular Ca2+ through dihydropyridine-sensitive Ca2+ channels plays an important role in this phenomenon.

Animals↗

PubMed1990

Effect of denervation of the phrenic nerve on the action of calcitonin gene-related peptide in rat diaphragm.

The effect of denervation on Calcitonin gene-related peptide (CGRP)-induced enhancement of the twitch contraction of skeletal muscle was studied. In rat diaphragm denervated 2 weeks previously, the basal twitch contraction induced by transmural stimulation was about twice that in control muscle, and the basal adenylate cyclase activity and cyclic AMP (cAMP) contents of the tissue were increased. This denervation did not affect the dose-dependent beta -adrenergic stimulation of twitch contraction, but abolished the CGRP-induced enhancement of twitch contraction. The latter phenomenon seems to be caused in part by decrease in CGRP-induced accumulation of cAMP over the basal level, because of increase in the basal cAMP level after denervation. The involvement of another inhibitory second messenger system coupled with CGRP receptors is discussed.

Adenylyl Cyclases↗

PubMed1990

Hyposmolarity stimulates myeloperoxidase exocytosis from human polymorphonuclear leukocytes.

Medium hyposmolarity induced in human polymorphonuclear leukocytes treated with cytochalasin B a rapid exocytosis of the lysosomal enzyme, myeloperoxidase (MPO), which was linearly proportional to the degree of hyposmolarity between a 5 and 30% decrease (r = 0.92, p less than 0.001). Cell viability was unaffected by the hyposmolarity. The kinetics of MPO exocytosis induced by opsonized zymosan (OZ) and hyposmolarity were indistinguishable; the combination of hyposmolarity and OZ was additive. Since hyposmolarity similarly stimulates a burst of hormone secretion by perifused adenohypophyseal and pancreatic islet cells, the authors suggest that hyposmolarity-induced exocytosis is a general cellular phenomenon.

Cell Survival↗

PubMed1990

Release of calcitonin gene-related peptide-like immunoreactive substance from neuromuscular junction by nerve excitation and its action on striated muscle.

In a rat phrenic nerve-hemidiaphragm preparation, calcitonin gene-related peptide (CGRP) increased the twitch contraction induced by nerve or transmural stimulation dose dependently. Either electrical or high K+ stimulation of the phrenic nerve caused release of a CGRP-like immunoreactive substance (CGRP-LIS) in a Ca2(+)-dependent manner. Electrical stimulation of the phrenic nerve also increased the cyclic AMP content in diaphragm. This increase was not observed in Ca2(+)-free medium and was blocked by antiserum against CGRP. These results indicate that excitation of the motor nerve causes release of CGRP-LIS at nerve terminals and that the released CGRP-LIS increases the cyclic AMP content of skeletal muscles and potentiates twitch contraction.

Animals↗

PubMed1990

Medium hyposmolarity stimulates prolactin secretion in GH4C1 cells by inducing an increase in cytosolic free calcium.

Extracellular hyposmolarity is a potent direct stimulus for hormone secretion for which a mechanism has not been delineated. The importance of plasmalemma Ca2+ permeability in this phenomenon in pituitary tumor-derived GH4C1 cells was evaluated by comparing the dynamics of changes in cytosolic free Ca2+ concentration [( Ca2+]i) with those of PRL secretion. At a normal physiological concentration of extracellular Ca2+ (1.5 mM), hyposmolarity induced a striking rise in both [Ca2+]i and PRL secretion, which was proportional to the stimulus between 0.50% reduction in medium osmolarity. Thirty percent hyposmolarity induced a 3-fold rise in [Ca2+]i and a 5-fold rise in PRL secretion above the basal level. These effects did not occur in cells incubated in a medium with a Ca2+ concentration lower than 30 microM. In cells incubated in 1.5 mM Ca2+, the Ca2(+)-channel antagonists, nifedipine and verapamil, significantly inhibited hyposmolar-induced increases in [Ca2+]i and PRL secretion. These data suggest that in GH4C1 cells medium hyposmolarity causes a burst of PRL secretion that depends on a similar preceding rise in [Ca2+]i produced by extracellular Ca2+ influx, most of which passes through dihydropyridine-sensitive Ca2(+)-channels.

Animals↗

PubMed1990

Evidence that ethanol induces prolactin secretion in GH4C1 cells by producing cell swelling with resultant calcium influx.

Although acute exposure to ethanol has been reported to affect hormone secretion, the data are sometimes conflicting, and the mechanism of action of ethanol is unclear. We have examined in GH4C1 cells the effect of isotonic ethanol on cell volume measured with a Coulter counter, the cytosolic Ca2+ concentration ([Ca2+]i) monitored with fura-2, and PRL secretion analyzed in a perifusion system. Isotonic ethanol caused prompt cell swelling and an explosive rise in both [Ca2+]i and PRL secretion proportional to the concentration of ethanol between 5-120 mM. The increases in both [Ca2+]i and PRL secretion induced by 80 mM isotonic ethanol were essentially abolished by removal of medium Ca2+ or by nifedipine; the nifedipine IC50 was approximately 20 nM. Cell swelling induced by hyposmolarity or isotonic urea similarly increased both [Ca2+]i and PRL secretion. Hypertonic ethanol did not cause cell swelling and was ineffective in inducing an increase in either [Ca2+]i or PRL secretion. These data suggest that in GH4C1 cells a major mechanism by which ethanol stimulates PRL secretion is to induce cell swelling, thus producing enhanced Ca2+ influx through dihydropyridine-sensitive Ca2+ channels.

Animals↗

PubMed1990

Role of extracellular calcium and calmodulin in prolactin secretion induced by hyposmolarity, thyrotropin-releasing hormone, and high K+ in GH4C1 cells.

The mechanism by which 30% medium hyposmolarity induces PRL secretion by GH4C1 cells was compared with that induced by 100 nmol/l TRH or 30 mmol/l K+. Removing medium Ca2+, blocking Ca2+ channels with 50 mumol/l verapamil, or inhibiting calmodulin activation with 20 mumol/l trifluoperazine, 10 mumol/l chlorpromazine or 10 mumol/l pimozide almost completely blocked hyposmolarity-induced secretion. The smooth muscle relaxant, W-7, which is believed relatively specific in inhibiting the Ca2(+)-calmodulin interaction, depressed hyposmolarity-induced PRL secretion in a dose-dependent manner (r = -0.991, p less than 0.01). The above drugs also blocked or decreased high K(+)-induced secretion, but had much less effect on TRH-induced secretion. Secretion induced by TRH, hyposmolarity, or high K+ was optimal at pH 7.3-7.65 and was significantly depressed at pH 6.0 or 8.0, indicating that release of hormone induced by all 3 stimuli is due to an active cell process requiring a physiologic extracellular pH and is not produced by nonspecific cell toxicity. The data suggest hyposmolarity and high K+ may share some similarities in their mechanism of stimulating secretion, which is different from that of TRH.

Animals↗

PubMed1989

Clinical evaluation of the 99mTc-CPI myocardial perfusion imaging.

99mTc-CPI myocardial perfusion scintigraphy including planar images in 35 patients and SPECT images in 16 patients has been studied. Scintigraphic data revealed that high quality 99mTc-CPI myocardial perfusion images were obtained. The sensitivity and specificity of 99mTc-CPI planar images in detecting CAD was 92% and 80% respectively. There was no significant difference in sensitivity for detecting CAD between planar and SPECT. However, the specificity of SPECT was much better than that of planar imaging.

Adult↗

PubMed1989

A vector that expresses secreted proteins on the cell surface.

A new vector, CDM8PI, has been constructed. It was derived from the plasmid expression vector CDM8, which has been used in the epitope-loss mutant isolation technique to map the epitopes on cell-surface proteins. The new vector allows the production of fusion proteins between normally secreted proteins and the membrane anchor moiety from a cell-surface protein, LFA-3, thereby expressing the fusion proteins on the cell surface. The vector extends the application of the epitope-loss mutant isolation technique to secreted proteins. The vector also allows the easy recovery of mutated proteins in unfused forms after the immunoselection and characterization.

Amino Acid Sequence↗

PubMed1989

Adolescent pregnancy: associations among body weight, zinc nutriture, and pregnancy outcome.

In a double-blind zinc trial in low-income, pregnant adolescents thought to be at risk for poor zinc nutriture, subjects were randomly assigned to receive 30 mg zinc (gluconate) or placebo. Response to zinc was related to maternal weight. Infants of normal-weight mothers given zinc had reduced rates of prematurity (p = 0.05) and assisted respiration (p = 0.006). Underweight multiparas given zinc had longer gestational lengths (p = 0.008) than did subjects given the placebo. Multiple stepwise regression analysis, used to identify predictors of infant size, revealed that 14-26% more variance was accounted for in the zinc than in the placebo group. Except for gestational age, the predictors selected were entirely different in the two groups. The zinc group had a positive toxemia screen more often, which did not appear to affect outcome. Zinc supplementation improved pregnancy outcome in normal-weight women and in underweight multiparas. The nonresponse in underweight primiparas was perhaps due to multiple limiting factors.

Adolescent↗