Effects of bromocriptine on prolactin release, electrical membrane properties and transmembrane Ca2+ fluxes in cultured rat pituitary adenoma cells

1986 ◽  
Vol 111 (2) ◽  
pp. 185-192 ◽  
Author(s):  
P. W. Johansen ◽  
O. Sand ◽  
J. G. Iversen ◽  
E. Haug ◽  
K. M. Gautvik
Keyword(s):  
Pituitary Adenoma ◽  
Action Potentials ◽  
Inhibitory Effect ◽  
Membrane Properties ◽  
Free Solution ◽  
Prolactin Release ◽  
Clonal Strain ◽  
Rat Pituitary ◽  
Basal Release ◽  
Voltage Dependent

Abstract. The effects of the dopamine (DA) agonist bromocriptine on prolactin (Prl) release, electrical membrane properties and transmembrane Ca2 + fluxes have been studied in a clonal strain of rat pituitary adenoma cells (GH3). These cells generate Ca2+ dependent action potentials, and produce and secrete spontaneously both Prl and growth hormone. Prl release stimulated by thyroliberin (TRH) and elevated extracellular K+ concentration was completely blocked by bromocriptine, whereas the basal release was only moderately affected. The TRH and K+ evoked Prl release were half maximally inhibited by bromocriptine at 5–10 and 10–50 μm, respectively. The normal biphasic membrane response to TRH and the depolarizing effect of elevated K+ concentration were not altered by bromocriptine, whereas the Ca2+-spikes in Na+-free solution were suppressed by the drug. We therefore suggest that bromocriptine blocks the voltage sensitive Ca2+-channels of GH3 cells. In agreement with this notion, bromocriptine also suppressed the basal and TRH induced 45Ca2+ efflux from preloaded cells. We conclude that the inhibitory effect of bromocriptine on the voltage dependent Ca2+-channels is an important mechanism responsible for suppression of Prl release.

Effects of trifluoperazine on prolactin release and cyclic AMP formation and degradation in GH4C1 pituitary cells

1987 ◽  
Vol 116 (1) ◽  
pp. 27-35
Author(s):  
Kjersti Sletholt ◽  
Jan Gordeladze ◽  
Egil Haug ◽  
Kaare M. Gautvik
Keyword(s):  
Inhibitory Effect ◽  
Pituitary Cells ◽  
Hormone Release ◽  
Prolactin Release ◽  
Camp Phosphodiesterase ◽  
Calmodulin Antagonist ◽  
Adenyl Cyclase Activity ◽  
Biphasic Effect ◽  
Basal Release ◽  
Dose Dependent

Abstract. In GH4C1 cells, the calmodulin antagonist trifluoperazine (TFP) showed a dose-dependent, biphasic effect on the basal release of PRL. An inhibition of PRL release was observed with 15–50 μmol/l TFP, whereas a concentration of 100 μmol/l and above had a stimulatory effect. The increase in basal hormone release evoked by TRH (1 μmol/l) and high extracellular concentration of K+ (50 mmol/l) was eliminated by 30 μmol/l TFP. The stimulatory effect of 100 μmol/l TFP on basal hormone release was not affected by addition of TRH (1 μmol/l) or K+ (50 mmol/l). The Ca2+ antagonists Co2+ (5 mmol/l) and verapamil (100 μmol/l), and the Ca2+ chelator EgTA (4 mmol/l) abolished the stimulatory effect of TRH (1 μmol/l) and of K+ (50 mmol/l on PRL release, whereas only Co2+ inhibited the stimulation caused by 100 μmol/l TFP. TFP (75 μmol/l) caused a transient increase in the concentration of cellular cAMP. Incubation of intact GH4C1 cells with TFP (75 μmol/l), had an inhibitory effect on both the low and the high affinity form of cAMP phosphodiesterase. Basal as well as TRH-stimulated adenyl cyclase activity were inhibited by TFP, and this effect was counteracted by addition of calmodulin.

Internal cesium ions block various K conductances in spinal motoneurons

1981 ◽  
Vol 59 (12) ◽  
pp. 1280-1284 ◽  
Author(s):  
E. Puil ◽  
R. Werman
Keyword(s):  
Action Potentials ◽  
Considerable Increase ◽  
Membrane Conductance ◽  
Membrane Properties ◽  
Resting Potential ◽  
Large Reduction ◽  
Spinal Motoneurons ◽  
Spike Generation ◽  
Cesium Ions ◽  
Voltage Dependent

Conventional intracellular recording with low resistance electrodes was used to examine the effects of iontophoretic injections of Cs+ ions (30–200 nA for 30–500 s) into spinal motoneurons of cats anesthetized with pentobarbital and paralyzed with gallamine. The most striking effects of internal Cs+ were a great prolongation of the falling phase of action potentials, a large reduction in the amplitude of their afterhyperpolarizations, and a considerable increase in the size of delayed depolarizations. A reduction of resting membrane conductance (up to half of control values) and a small increase in membrane potential usually were evident. Although the rate of rise and amplitude of spikes sometimes were increased, the above effects on membrane properties usually were accompanied by block of antidromic invasion or synaptic spike generation, and inactivation of directly evoked spikes. Recovery of spike genesis was very rapid but the prolongation of spikes and other effects of Cs+ lasted 4–35 min, depending on the amount of Cs+ application. Larger injections of Cs+ resulted in greater depolarizations of up to 13 mV. It is concluded that internal Cs+ ions block voltage-dependent K+ conductance of spike repolarization, the Ca2+-activated K+ conductance responsible for the afterhyperpolarization, and some of the K+ conductance responsible for the resting potential. It is suggested that the enhanced delayed depolarization may result from a Cs+-blockade of an early outward K+ current which would unmask an inward current of Ca2+ ions.

Mechanisms for signal transformation in lemniscal auditory thalamus

1996 ◽  
Vol 76 (6) ◽  
pp. 3597-3608 ◽  
Author(s):  
F. Tennigkeit ◽  
D. W. Schwarz ◽  
E. Puil
Keyword(s):  
Action Potentials ◽  
Input Resistance ◽  
Membrane Properties ◽  
High Threshold ◽  
Tonic Firing ◽  
Sensory Stimuli ◽  
Current Pulses ◽  
Type K ◽  
Voltage Dependent ◽  
Medial Geniculate

1. During alertness, lemniscal thalamocortical neurons in the ventral medial geniculate body (MGBv) encode sound signals by firing action potentials in a tonic mode. When they are in a burst firing mode, characteristic of thalamic neurons during some sleep states, the same stimuli may have an alerting function, leading to conscious perception of sound. We investigated the intrinsic membrane properties of MGBv neurons in search of mechanisms that enable them to convert from burst to tonic firing modes, allowing accurate signal coding of sensory stimuli. 2. We studied thalamocortical relay neurons and identified neurons morphologically with injected N-(2-aminoethyl) biotinamide hydrochloride in in vitro slice preparations of young rats. With the use of the whole cell recording method, we examined the contributions of distinct conductances to voltage responses evoked by current pulses. The neurons (n = 74) displayed a narrow range of resting potentials (-68 +/- 4 mV, mean +/- SD) and an average input resistance of 226 +/- 100 M omega. The membrane time constant was 40 +/- 17.6 ms and the action potential threshold was -51.6 +/- 3 mV. 3. Injections of hyperpolarizing current pulses from rest revealed an inward rectification produced by two voltage-dependent components. A fast component, sensitive to blockade with Ba2+ (100–200 microM), was attributed to an inward rectifier, IIR. Such applications also increased input resistance and depolarized neurons, consistent with a blockade of various K+ conductances. Application of Ba2+ often unmasked another voltage-dependent rectification with a slower time course. The second component was sensitive to blockade with Cs+ (1.5 mM), reminiscent of a hyperpolarization-activated current, IH. 4. Depolarizing pulses from rest produced ramp-shaped voltage responses that led to delayed tonic firing. Blockade of Na+ conductances by tetrodotoxin (TTX, 300–600 nM), or extracellular replacement of Ca2+ with Mg2+ (with TTX present), reduced the slope of the ramp and the overall depolarizing response. Application of 4-aminopyridine (4-AP, 100 microM), a blocker of A-type K+ conductances, increased input resistance and the overall depolarizing response. The voltage ramp therefore represents a complex rectification due to voltage-dependent contributions of persistent Na-, Ca2+, and K+ conductances. 5. Depolarizing pulses from potentials of less than -75 mV evoked phasic burst responses, consisting of one to seven action potentials riding on a low-threshold spike (LTS). The LTS was absent in low extracellular Ca2+ conditions and was blocked by application of Ni2+ (0.6 mM), but not by Cd2+ (50 microM). Similar depolarization from less than -80 mV evoked several action potentials, often followed by a TTX-resistant high-threshold spike (HTS) of longer duration. Firing of HTSs always occurred during 4-AP (100 microM) application, inferring that, normally, A-type K+ conductances may control ability to fire an HTS. As in the LTS, a Ca2+ current is a major participant in the HTS because extracellular replacement of Ca2+ with Mg2+ or application of Cd2+ (50 microM) blocked its genesis. After TTX blockade of Na+ conductances, “tonic firing” of HTSs occurred during depolarization above -45 mV. 6. During tonic firing evoked by current pulses, the second and subsequent spikes were longer in duration than the initial action potentials. Low extracellular concentrations of Ca2+ or Cd2+ (50 microM) application reduced the durations of the nonprimary spikes, inferring a contribution of high-threshold voltage-dependent Ca2+ conductances to their repolarizing phase. Also, K+ conductances may contribute to spike repolarization, because 4-AP (100 microM) or tetraethylammonium (2 mM) application led to prolonged action potentials and the generation of plateau potentials. A fast afterhyperpolarization, likely mediated by a Ca(2+)-dependent K+ conductance, limited the tonic firing. Such conductances, therefore, may regulate the re

scholarly journals The effects of microenvironment on the redifferentiation of regenerating neurones: neurite architecture, acetylcholine receptors and Ca2+ channel distribution

1987 ◽  
Vol 132 (1) ◽  
pp. 111-131
Author(s):  
M. E. Spira ◽  
D. Zeldes ◽  
B. Hochner ◽  
A. Dormann
Keyword(s):  
Action Potentials ◽  
Acetylcholine Receptors ◽  
Membrane Properties ◽  
Environmental Cues ◽  
Freezing And Thawing ◽  
Intrinsic Factors ◽  
Extrinsic Cues ◽  
Voltage Dependent ◽  
Synaptic Receptors ◽  
Ca2 Channels

Severed adult neurones, which are capable of regrowth, encounter different microenvironments from those encountered during development. Moreover, adult neurones may respond in a different manner from developing neurones to the same environmental cues. Thus, the recovery of the integrative and transmission capabilities (which depend on the neuronal architecture, passive and active membrane properties, and synaptic receptor distribution) by a regenerating adult neurone may not be complete. In the present review, we examine several aspects of the outcome of the interaction between the microenvironment and regrowing neurones using the cockroach giant interneurones (GINs) as a model system. We demonstrate that whereas extrinsic cues govern the morphological redifferentiation and distribution of synaptic receptors, the distribution of voltage-dependent Ca2+ channels is to a large extent determined by intrinsic factors. The pathway of regrowth and the architecture of regenerating GINs were studied by examination of intracellularly stained fibres. The environments provided by the connectives and ganglia are different. The elongating sprouts in the connective appeared as smooth cylinders. Within the ganglionic domain, the main longitudinal sprouts emitted neurites which extended and branched into the neuropile. The local cues for branching of neurites were eliminated by freezing and thawing of the ganglia prior to the arrival of the growing tips. The failure to extend neurites under these conditions is attributed to the elimination of extrinsic signals for morphological redifferentiation of the fibres, since the same fibres emit neurites in anterior ganglia which have not been subjected to freezing and thawing. The distribution of acetylcholine receptors (AChRs) on the GINs was mapped by ionophoretic application of ACh. In both the intact and regenerating GINs receptors were located only on the neurites. Freezing and thawing of a ganglion eliminated the local signals for insertion and/or activation of AChRs on the neurites. Thus, both the morphological redifferentiation and the distribution of AChRs are affected by the microenvironment. Voltage-dependent Ca2+ channels were detected after intracellular injection of tetraethylammonium into the GIN and in the presence of tetrodotoxin (TTX) and Ba2+ in the extracellular space. The regrowing axon tips always revealed large barium action potentials independent of the CNS microenvironment. This observation is consistent with the hypothesis that Ca2+ plays an important role in the growth process. However, increased Ba2+ responsiveness was also observed in axonal segments proximal to the region of neuronal extension.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Curcumin sensitizes prolactinoma to bromocriptine by activating the ERK/EGR1 and inhibiting AKT/GSK3β signaling pathway

2021 ◽  
Author(s):  
Chao Tang ◽  
Junhao Zhu ◽  
Feng Yuan ◽  
Jin Yang ◽  
Xiangming Cai ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Expression Profiles ◽  
Inhibitory Effect ◽  
Growth Inhibitory Effect ◽  
Growth Inhibitory ◽  
Test Protein ◽  
Rat Pituitary

Abstract Background Although bromocriptine (BRC) as first-line drugs are recommended for treating patients with prolactinoma, a minority of patients with prolactinoma resistance to BRC. Curcumin (Cur) has been shown to inhibit proliferation of prolactinoma cell lines. The aim of this study is to investigate whether Cur could enhance the growth-inhibitory effect of BRC resistance on prolactinoma cell lines and its possible mechanism. Methods CCK-8 kit was used to test cell growth. Cell-cycle analysis and apoptosis was performed by flow cytometry. Electron microscopy was used to test autophagosome. The mRNA expression profiles were analysed using the Affymetrix Gene-Chip array. Western blotting was used to test protein expression. The SPSS version 17.0 software was applied for statistical analysis. Results Our data showed that Cur enhanced the growth-inhibitory effect of BRC on GH3 and MMQ cell proliferation. BRC and Cur both induced cell apoptosis, and Cur could significantly increase the apoptosis of BRC on pituitary adenoma cells through the ERK/EGR1 signaling pathway. Moreover, Cur could enhance the autophagic cell death (ACD) of BRC on tumor cell by inhibiting the AKT/GSK3β signaling pathway. The same results were confirmed in vivo study. Conclusion Cur sensitizes rat pituitary adenoma cell to BRC by activating the ERK/EGR1 and inhibiting AKT/GSK3β signaling pathway.

scholarly journals The mechanism of tubocurarine action on mechanoreceptor channels in the protozoan Stentor coeruleus

1985 ◽  
Vol 117 (1) ◽  
pp. 215-235
Author(s):  
D. C. Wood
Keyword(s):  
Mechanical Stimulation ◽  
Action Potentials ◽  
Response Probability ◽  
Linear Increase ◽  
Membrane Properties ◽  
Reversible Binding ◽  
Exponential Component ◽  
Voltage Dependent ◽  
Stentor Coeruleus ◽  
Highly Correlated

(+)-Tubocurarine (TC) decreases the probability that the protozoan, Stentor coeruleus Ehrenberg, will contract in response to mechanical stimulation, because it selectively depresses mechanoreceptor currents. Resting membrane properties and action potentials are not significantly altered by the drug. Stentor incubated in media containing radioactively labelled TC (TC*) retain TC* after extensive washing despite a rather high apparent KD (19.7 mumol l-1). The incubation curve for TC* binding exhibits an initial exponential rise followed by a linear increase. Wash-out of bound TC* and elimination of the exponential component of the incubation curve is observed if the TC* incubation is followed by a 5-s exposure to 8% urea; therefore, the exponential component represents a reversible binding process. TC* binding in the exponential component is highly correlated (r less than −0.96) with the depression in receptor current and response probability when incubation time, drug concentration and drug (gallamine, TC, decamethonium and succinylcholine) are varied. These correlations suggest that the exponential binding is to functional mechanoreceptors. Mechanoreceptor currents are decreased by hyperpolarization and increased by depolarization, indicating that the mechanoreceptor channel is voltage-dependent. At hyperpolarized potentials the channels are in a form (the U form) which cannot be opened by mechanical stimulation; at depolarized potentials they are in a form (the R form) which can be opened. TC appears to bind to the U form with higher affinity than to the R form, since depolarization reduces the amount of bound TC* and relieves the depression of mechanoreceptor current produced by TC.

Voltage-dependent blockade in Na+-dependent action potentials after β1- and H2-receptor stimulation in mammalian ventricular myocardium

1988 ◽  
Vol 66 (10) ◽  
pp. 1291-1296 ◽  
Author(s):  
A. M. Gillis ◽  
M. Kohlhardt
Keyword(s):  
Action Potentials ◽  
Ventricular Myocardium ◽  
Inhibitory Effect ◽  
Receptor Blocker ◽  
Control Value ◽  
Relationship Analysis ◽  
Adrenoceptor Agonist ◽  
Voltage Dependent ◽  
Initial Control ◽  
Β Receptor

In isolated papillary muscles of guinea pigs, the influence of isoproterenol, histamine, theophylline, and phenylephrine on the maximal rate of rise [Formula: see text] of Na+-dependent action potentials and on isometric contractile force was studied under rested state conditions. Isoproterenol (1 × 10−7 mol/L), histamine (2 × 10−5 mol/L), and theophylline (2 × 10−3 mol/L) shifted the voltage dependence of [Formula: see text] into the hyperpolarizing direction and, consequently, led to a voltage-dependent [Formula: see text] blockade. The α-adrenoceptor agonist phenylephrine, on the other hand, proved to be ineffective in depressing [Formula: see text]. The β-receptor blocker pindolol (4 × 10−6 mol/L) or the H2-receptor blocker cimetidine (4 × 10−5 mol/L) abolished the inhibitory effects of isoproterenol and histamine, respectively, and caused [Formula: see text] to return to the initial control value. A concentration–response relationship analysis at −65 mV revealed that isoproterenol exerted only a weak inhibitory effect on [Formula: see text] compared with its positive inotropic action. The IC50 value of the former effect amounted to approximately 5 × 10−6 mol/L, but the EC50 value of the latter effect was 4 × 10−8 mol/L. It is, therefore, concluded that, in physiologically relevant concentrations, β-adrenergic agonists are unlikely to significantly modulate Na+-dependent excitability even in partially depolarized myocardium.

Role of Ca2+ and Na+ on luteinizing hormone release from the calf pituitary

1988 ◽  
Vol 255 (4) ◽  
pp. E469-E474
Author(s):  
J. P. Kile ◽  
M. S. Amoss
Keyword(s):  
Luteinizing Hormone ◽  
Ionophore A23187 ◽  
Channel Blockers ◽  
Hormone Release ◽  
Primary Cells ◽  
Rat Pituitary ◽  
Voltage Dependent ◽  
Lh Release ◽  
Ca2 Channels

It has been proposed that gonadotropin-releasing hormone (GnRH) stimulates Ca2+ entry by activation of voltage-independent, receptor-mediated Ca2+ channels in the rat gonadotroph. Little work has been done on the role of calcium in GnRH-induced luteinizing hormone (LH) release in species other than the rat. Therefore, this study was done to compare the effects of agents that alter Ca2+ or Na+ entry on LH release from calf anterior pituitary primary cells in culture. GnRH (100 ng/ml), Ca2+ ionophore A23187 (2.5 microM), and the depolarizing agent ouabain (0.1-10 microM) all produced significant increases (P less than 0.05) in LH release; these effects were significantly reduced when the cells were preincubated with the organic Ca2+ channel blockers nifedipine (1-10 microM) and verapamil (1-10 microM) and with Co2+ (0.01-1 mM). The effect of ouabain was inhibited by tetrodotoxin (TTX; 1-10 nM) as well as by nifedipine at 0.1-10 microM. In contrast to its effect on rat pituitary LH release, TTX significantly inhibited GnRH-stimulated LH release at 1-100 nM. These results suggest that GnRH-induced LH release may employ Ca2+ as a second messenger in bovine gonadotrophs and support recent speculation that GnRH-induced Ca2+ mobilization may in part be voltage dependent.

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