Biomedical subjects

C Schöfl

Publications and source records attributed to C Schöfl.

36 records · Page 2Linked to original sources

PubMed1996

CYCLIC adenosine 3',5'-monophosphate potentiates Ca2+ signaling and insulin secretion by phospholipase C-linked hormones in HIT cells.

Neurotransmitters and hormones, by binding to receptors linked to adenylate cyclase or phospholipase C (PLC), increase cytosolic free Ca2+ and potentiate glucose-induced insulin release from beta-cells. Interactions between both signaling pathways may occur and be of relevance to the regulation of insulin secretion. We demonstrate here that in single insulin-secreting HIT cells, forskolin and 8-bromo-cAMP, which stimulate Ca2+ influx through voltage-dependent Ca2+ channels (VDCC), cause a marked increase in the frequency, amplitude, and duration of Ca2+ transients evoked by hormones linked to PLC, such as arginine vasopressin (AVP) or bombesin. Forskolin also potentiates AVP- or bombesin-induced insulin secretion from populations of HIT cells in the presence of elevated glucose (10 mM). BAY K 8644, an activator of VDCC, mimicked the effects of elevated cAMP on both AVP- and bombesin-induced Ca2+ transients and insulin release, which suggests that enhanced Ca2+ influx through VDCC activated by cAMP-dependent mechanisms underlies the positive interactions of both signaling pathways on Ca2+ signaling and insulin secretion. Physiologically, synergistic cross-signaling between the cAMP- and Ca2+ -phosphoinositide signaling pathway could be important for the regulation of insulin release under conditions where extracellular glucose is high and beta-cells are exposed to multiple stimuli activating adenylate cyclase or PLC at the same time.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1995

Extracellular nucleotides increase cytosolic free calcium by activating P2u-receptors in single human gastric mucous cells.

In single human gastric mucous cells extracellular ATP, ATP-gamma-S, ADP and UTP at micromolar concentrations caused a biphasic increase in [Ca2+]i. Consistent with a P2u-receptor the rank-order of potency was ATP > or = UTP > ATP-gamma-S > ADP, and cross-desensitization of the Ca2+ responses occurred between ATP and UTP. The initial transient peak in [Ca2+]i was resistant to extracellular Ca2+ depletion which demonstrates mobilization of internal Ca2+. By contrast, the sustained plateau phase required influx of external Ca2+. Ca2+ influx occurs most likely through a capacitative Ca2+ entry mechanism, which was shown to exist in these cells by experiments performed with thapsigargin. Thus, extracellular ATP and UTP activate a common P2u-receptor most likely coupled to the Ca(2+)-phosphatidylinositol signalling cascade. Extracellular nucleotides from various sources might be an important factor in the regulation of human gastric mucous cells.

Adenosine Diphosphate↗

PubMed1995

Extracellular ATP and UTP increase cytosolic free calcium by activating a common P2u-receptor in single human thyrocytes.

In single human thyrocytes extracellular ATP, ATP-gamma-S, ADP and UTP caused a concentration-dependent biphasic increase in [Ca2+]i. Consistent with a P2u-receptor the rank-order of potency was ATP = UTP > ATP-gamma-S > ADP, and cross-desensitization of the Ca2+ responses occurred between ATP and UTP. The initial transient peak in [Ca2+]i was resistant to extracellular Ca2+ depletion which demonstrates mobilisation of internal Ca2+ by IP3 whose formation was rapidly enhanced by ATP and UTP. By contrast, the sustained plateau phase required influx of external Ca2+. Ca2+ influx occurs most likely through a capacitative Ca2+ entry mechanism, which was shown to exist in these cells by experiments performed with thapsigargin. Thus, low micromolar concentrations of extracellular ATP and UTP activate a common P2u-receptor coupled to the C(a2+)-phosphatidylinositol signalling cascade in human thyrocytes. This indicates that extracellular nucleotides from various sources might play an important role in human thyroid physiology.

Adenosine Triphosphate↗

PubMed1995

Cognitive functioning in experimental hypoglycaemia assessed with event-related potentials.

Cognitive effects of experimentally induced hypoglycaemia were investigated by event-related brain potentials (ERPs) in auditory and visual classification tasks. In a cross-over design eight healthy male subjects (age 22-27 years) were studied under control conditions or following administration of 0.15 IU insulin kg-1. The ERPs showed preserved early cortical components, while the N2 component was greatly reduced in both modalities. P3 components did not show an influence of hypoglycemia. These results suggest that the cognitive deficits are due to an impairment of automatic feature extraction from the stimuli.

Adult↗

PubMed1995

Vasopressin induces frequency-modulated repetitive calcium transients in single insulin-secreting hit cells.

Ca2+ is central to the stimulation of insulin secretion from pancreatic beta-cells. Arginine-vasopressin (AVP) may participate in the modulation of insulin release. In the present study, the AVP-induced changes in cytosolic free Ca2+ ([Ca2+]i) were investigated in single fura-2 loaded insulin-secreting HIT cells. Stimulation with AVP (0.1-5 nM) caused repetitive Ca2+ transients. The frequency but not the amplitude of the Ca2+ transients was modulated by the concentration of AVP. High concentrations of AVP (10-100 nM) triggered a biphasic rise in [Ca2+]i. In Ca(2+)-free medium AVP caused only one or two Ca2+ transients. Withdrawal of extracellular Ca2+ rapidly abolished the AVP-induced Ca2+ transients in all cells tested. The Ca2+ channel blocker, verapamil (50 microM), reduced amplitude and frequency of the Ca2+ transients by about 25% and 60%, respectively, and terminated the Ca2+ transients in 2 of 6 cells. When HIT cells were incubated in Ca(2+)-free medium, and extracellular Ca2+ was restored, there was a small increase in [Ca2+]i. If, however, the agonist-sensitive Ca2+ pool was functionally depleted by repetitive stimulation with high concentrations of AVP or thapsigargin in Ca(2+)-free medium before extracellular Ca2+ was restored, an agonist-independent increase in [Ca2+]i was observed, which was transiently larger than in the control cells, and was mainly preserved in the presence of verapamil. Thus, depletion of the agonist-sensitive Ca2+ pool enhances the influx of extracellular Ca2+ through a Ca2+ entry mechanism independent from verapamil-sensitive voltage-dependent Ca2+ channels (VDCC).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Inhibition by antidepressant drugs of cyclic AMP response element-binding protein/cyclic AMP response element-directed gene transcription.

Clinical observations agree that antidepressant drugs are effective only after a lag phase of 1-3 weeks. This delay could be explained at the molecular level by an action on gene transcription. Transcription of many genes is directed by the cAMP/Ca(2+)-responsive element (CRE) and its cognate transcription factor CRE-binding protein (CREB). Membrane depolarization and cAMP induce the phosphorylation of CREB at Ser-119 and thereby stimulate the transcriptional activity of CREB. The effect of antidepressant drugs on CREB/CRE-directed gene transcription was investigated using transient transfections of reporter fusion genes in HIT and PC-12 cells. Clomipramine, imipramine, fluoxetine, doxepin, desipramine, amitriptyline, maprotiline, mianserin, and trazodone inhibited CRE-directed gene transcription that was stimulated by membrane depolarization, with IC50 values between 70 nM and 1.73 microM. Desipramine had no effect on transcription after stimulation by cAMP but blocked the synergistic effect of cAMP and membrane depolarization to the level of stimulation by cAMP alone. Upon membrane depolarization, desipramine reduced the phosphorylation of CREB at Ser-119 and also blocked the depolarization-induced increase in the intracellular free Ca2+ concentration in HIT cells. Thus, by interfering with the depolarization-induced activation of the transcription factor CREB, antidepressant drugs can inhibit CRE-directed gene transcription, which could underlie the pharmacological effects of these clinically important drugs.

Animals↗

PubMed1995

[Pulsatile hormone secretion for control of target organs].

Pulsatile secretion of hormones are observed in many endocrine systems. Here we discuss the significance of pulsatile patterns of hormone secretion for the regulation of endocrine target tissues in physiology and pathophysiology. New approaches to analyze endocrine rhythms are introduced that may enable to better define the temporal patterns of secretion relevant for the regulation of distinct processes in complex in vivo systems. This may lead to improved diagnostic and therapeutic strategies of endocrine diseases.

Animals↗

PubMed1993

Temporal patterns of alpha 1-receptor stimulation regulate amplitude and frequency of calcium transients.

The pulsatile release of neurotransmitters and many hormones might encode specific biological information according to temporal pattern. We tested this hypothesis by applying pulsed alpha 1-adrenoceptor stimulation to single aequorin-injected hepatocytes. The amplitude of free Ca2+ transients induced by rapid phenylephrine pulses (20-s interpulse interval) and continuous stimulation was similar (approximately 640 nM) but increased to approximately 1,000 nM as the interpulse interval was increased to 120 s. The same overall response was maintained despite a 13-fold reduction in average phenylephrine concentration. Some regimes of pulsed phenylephrine stimulation could give a higher frequency of pulsed phenylephrine stimulation could give a higher frequency of free calcium oscillations than continuous stimulation, or more rapid stimulation when some agonist pulses failed to elicit a free Ca2+ transient. For the same average phenylephrine concentration (0.3-0.6 microM), pulsed regimes could result in significantly higher frequencies and integrated responses than constant application. The lags between phenylephrine pulses and free Ca2+ transients reduced as the period between pulses increased. The amplitude and lag data are consistent with a refractory period of 18 s and a recovery phase with a time constant of approximately 100 s, perhaps corresponding to dephosphorylation of alpha 1-adrenoceptors phosphorylated by protein kinase C during each free Ca2+ transient.

Adrenergic alpha-Agonists↗

PubMed1992

Evidence for P2-purinoceptors on human osteoblast-like cells.

ATP released from damaged cells or by controlled secretion could be an important factor in the formation or remodeling of bone. In a variety of other tissues ATP has been shown to control cellular processes by acting on P2-purinoceptors and activating the calcium signaling pathway. Here we demonstrate for the first time that extracellular ATP increases the intracellular free calcium [Ca2+]i concentration in normal human osteoblasts and in SaOS-2 cells, a human osteosarcoma-derived cell line, but not in ROS 17/2.8 cells. The ATP-induced increase in [Ca2+]i was dose dependent, and the concentrations of ATP required were similar to those reported to regulate cellular functions in other cell types. Although ATP is metabolized rapidly by bone cells, the effects on [Ca2+]i appeared to be mediated directly by ATP rather than one of its metabolites. Adenosine 3-thiotriphosphate, a nonhydrolyzable analog of ATP, induced similar changes in [Ca2+]i. This indicates that P2-purinoceptors are present on osteoblast-like cells and that extracellular ATP from various sources might be an important factor in the regulation of osteoblast functions.

Adenosine Triphosphate↗

PubMed1991

Measurement of intracellular Ca2+ in single aequorin-injected and suspensions of fura-2-loaded ROS 17/2.8 cells and normal human osteoblasts. Effect of parathyroid hormone.

It is known that parathyroid hormone (PTH) activates the cyclic AMP (cAMP) signalling pathway in osteoblasts. In recent years it has been suggested that an elevation of the intracellular free Ca2+ concentration ([Ca2+]i) may also be involved in the regulation of osteoblast function by PTH. However, this remains controversial. Here we investigated the effect of PTH on the [Ca2+]i of ROS 17/2.8 cells and normal human osteoblasts. The [Ca2+]i was measured in single aequorin-injected cells and in suspensions of cells loaded with fura-2. Human PTH-(1-38)-peptide (1-300 nM) had no effect on the [Ca2+]i in single aequorin-injected ROS 17/2.8 cells (n = 17) measured at various times after injection (1-20 h), or in suspensions of fura-2-loaded ROS 17/2.8 cells (n = 9). Ionomycin (1 microM) increased the [Ca2+]i in fura-2-loaded and single aequorin-injected ROS 17/2.8 cells by 285 +/- 60 nM (n = 9) and 312 +/- 99 nM (n = 6) respectively, indicating that both methods detect changes in [Ca2+]i with equal sensitivity. In contrast, human PTH-(1-38) (10-100 nM) markedly stimulated cAMP accumulation in ROS 17/2.8 cells. In single aequorin-injected normal human osteoblasts there was no change in the [Ca2+]i in response to 100 nM human PTH-(1-38) or 100 nM bovine PTH-(1-84) (n = 18). In contrast, in suspensions of normal human osteoblasts loaded with fura-2, an increase in [Ca2+]i in response to human PTH-(1-38) (100 nM) was found (60 +/- 28 nM; n = 6). Considerable variation in the magnitude of the response was observed between individual preparations and donors. These data indicate that PTH activates cAMP accumulation without affecting [Ca2+]i in ROS 17/2.8 cells and that PTH causes a rise in [Ca2+]i only in a small subset of normal human osteoblasts. We suggest that the Ca2+ response to PTH in osteoblasts is limited by the state of differentiation of the cells, and may be due either to the presence of a distinct Ca2(+)-mobilizing receptor or to a cAMP-mediated Ca2+ response.

Aequorin↗

PubMed1991

Frequency and amplitude enhancement of calcium transients by cyclic AMP in hepatocytes.

Interactions between signalling pathways such as the cyclic AMP and the Ca2+/phosphatidylinositol pathway may occur and be of major relevance in the regulation of cell function. We demonstrate here that cyclic-AMP-dependent mechanisms cause a marked increase in frequency and peak free Ca2+ of alpha 1-receptor-induced Ca2+ transients in single hepatocytes and lower the threshold for alpha 1-receptor agonists. Adrenaline at low physiological concentrations generates alpha 1-receptor-induced Ca2+ transients, which requires activation of the beta 2-receptor signalling pathway. We conclude that an interaction between the alpha 1-receptor signalling pathway and cyclic-AMP-dependent mechanisms activated by beta 2-receptor occupation is crucial to elicit a complete adrenergic response to adrenaline at physiological concentrations in rat hepatocytes.

Aequorin↗

PubMed1990

Aluminium perturbs oscillatory phosphoinositide-mediated calcium signalling in hormone-stimulated hepatocytes.

Aluminium is known to be toxic to cells from bone, brain and bone marrow but the molecular target(s) affected by Al3+ are not known. We show here that Al3+ disrupts the oscillatory free Ca2+ responses of hepatocytes exposed to the Ca2(+)-mobilizing agonist phenylephrine. Al3+ initially increases the frequency of the oscillations and later induces broad Ca2+ spikes lasting several minutes. These broad spikes persist after removal of both agonist and Al3+ from the medium. In the absence of agonist, Al3+ has no effect on free Ca2+. The data suggest that some component(s) of the receptor-phosphoinositide-Ca2+ signalling pathway might be the site at which Al3+ exerts toxic effects.

Animals↗

PubMed1988

Opioids and cytosolic calcium in rat anterior pituitary: dynorphin preparation showed LHRH-like action due to contamination.

The effect of dynorphin A-(1-13) (Dyn A-(1-13] and other opioids on the cytosolic free calcium concentration [(Ca2+]i) in rat anterior pituitary cells was examined using the fluorescent indicator fura-2. A commercial synthetic Dyn A-(1-13) preparation elevated [Ca2+]i. Results, which were obtained with receptor antagonists, and in LHRH receptor radioligand binding studies as well as by HPLC combined with LHRH radioimmunoassay, strongly suggest that this effect of the dynorphin preparation was due to contamination with a LHRH-like compound. Dyn A-(1-13), purified by HPLC, as well as Dyn A-(2-13), [Leu5]enkephalin, beta-endorphin, morphine, or U50,488H had no effect on [Ca2+]i. LHRH caused a rapid increase in [Ca2+]i by about 50 nM which was blocked by the LHRH antagonist, [D-pGlu1,D-Phe2,D-Trp3,6] LHRH.

Animals↗

PubMed1988

Arachidonic acid elevates cytosolic free calcium concentration in rat anterior pituitary cells.

Arachidonic acid is liberated from phospholipids by various hypothalamic releasing hormones and may be involved in stimulus-secretion coupling in rat adenohypophysis. In the present study, the effect of exogenous arachidonic acid on calcium homeostasis in rat anterior pituitary cells was investigated in vitro. Arachidonic acid markedly stimulated the release of various anterior pituitary hormones (beta-endorphin, luteinizing hormone, growth hormone). Arachidonic acid (10 mumol/l) decreased the initial rate of 45Ca2+ uptake. In cells prelabelled with 45Ca2+, arachidonic acid (10 mumol/l) decreased the exchangeable cell calcium content and increased the rate of 45Ca2+ extrusion. Cytosolic free calcium concentration [( Ca2+]i) was measured with the fluorescent indicator fura-2. Arachidonic acid markedly elevated [Ca2+]i. The concentration dependency of this effect (1 mumol/l and above) was similar to that on hormone secretion. Arachidonic acid (6 mumol/l) elevated [Ca2+]i by about 300 nmol/l, and arachidonic acid (10 mumol/l) raised [Ca2+]i into the micromolar range. The effect of arachidonic acid (3 mumol/l) on [Ca2+]i was not influenced by inhibitors of arachidonic acid metabolism (nordihydroguaiaretic acid, BW755C). In Ca2+-free media (Ca2+ omitted, EGTA 2 mmol/l), the effect of arachidonic acid (3 mumol/l) on [Ca2+]i was almost unimpaired, whereas the effect of arachidonic acid (10 mumol/l) was reduced. Thus, the secretagogue arachidonic acid induces calcium mobilization and an increase in cytosolic free calcium concentration. These actions further qualify arachidonic acid as a potential intracellular mediator of stimulus-induced hormone secretion from rat adenohypophysis.

Animals↗

PubMed1988

Potassium depolarization elevates cytosolic free calcium concentration in rat anterior pituitary cells through 1,4-dihydropyridine-sensitive, omega-conotoxin-insensitive calcium channels.

Changes in membrane potential may influence Ca2+-dependent functions through changes in cytosolic free calcium concentration [( Ca2+]i). This study characterized pharmacologically those voltage-dependent Ca2+ channels in normal rat anterior pituitary cells that are involved in the elevation of [Ca2+]i upon high potassium-induced membrane depolarization. The [Ca2+]i was monitored directly by means of the intracellularly trapped fluorescent indicator fura-2. The addition of K+ (6-100 mM) increased [Ca2+]i in a concentration-dependent manner. The fluorescent signal reached a peak within seconds and then decayed to form a new elevated plateau. K+ at the highest concentration used (100 mM) raised [Ca2+]i by about 450 nM. The K+-induced increase in [Ca2+]i was absent in a Ca2+-free medium. BAY K 8644, a 1,4-dihydropyridine Ca2+ channel agonist, also caused an increase in [Ca2+]i. The maximum response in [Ca2+]i upon stimulation with BAY K 8644 (100 nM) was about 40 nM. The half-maximally effective concentration of BAY K 8644 (100 nM) was about 20 nM. The response in [Ca2+]i upon BAY K 8644-stimulation was abolished in a Ca2+-free medium. Predepolarization with various K+ concentrations enhanced the effect of BAY K 8644 (1 microM) on [Ca2+]i. Pretreatment with BAY K 8644 (1 microM) enhanced the response in [Ca2+]i induced by K+ (25 mM). The addition of Mg2+ (30 mM) and nifedipine (1 microM) lowered the resting [Ca2+]i by about 40 and 20 nM, respectively. Mg2+, nifedipine, nimodipine, Gö 5438, verapamil, and diltiazem inhibited the K+ (25 mM)-induced increase in [Ca2+]i; the order of potency (and half-maximally inhibitory concentrations) were nimodipine = Gö 5438 = nifedipine (approximately 100 nM) greater than verapamil (900 nM) greater than diltiazem (greater than 10 microM) greater than Mg2+ (6 mM). Omega-Conotoxin (100 nM) did not inhibit the K+ (25 mM)-induced increase in [Ca2+]i. These data demonstrate that, over a wide range, membrane depolarization induced by high potassium concentration is indeed associated with increases in [Ca2+]i in normal rat anterior pituitary cells. This elevation of [Ca2+]i is mainly due to an influx of Ca2+ through 1,4-dihydropyridine-sensitive, omega-conotoxin-insensitive calcium channels (L-type).

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1987

Intracellular free calcium concentration in rat anterior pituitary cells as indicated by fura-2: effect of arginine-vasopressin.

Arginine-vasopressin (AVP) stimulates adrenocorticotropin and beta-endorphin release from corticotrophs of the anterior pituitary gland through mechanisms which are not initiated by an elevation of the cellular levels of adenosine-3',5'-cyclic-monophosphate. In the present study the effect of AVP on the cytoplasmic concentrations of free calcium ions in rat anterior pituitary cells was examined. Cytosolic free Ca2+ concentrations were monitored directly using the new, intracellularly trapped fluorescent indicator fura-2. In cells incubated in medium containing 1.3 mmol/l Ca2+, AVP (100 nmol/l) caused an immediate elevation of the cytoplasmic Ca2+ concentration by about 50 nmol/l (P less than 0.001). The intracellular Ca2+ levels remained elevated during the observation period of 2-3 min. This effect of AVP was blocked by a specific vasopressin antagonist. By contrast, the glucocorticoid dexamethasone did not affect the AVP-induced elevation of cytosolic Ca2+ concentration. When the cells were incubated in Ca2+-free medium (Ca2+ omitted, EGTA 2 mmol/l), the AVP-induced as well as the K+ depolarization-induced increase in free cytoplasmic Ca2+ were abolished, whereas the ionophore ionomycin evoked a rapid transient elevation of free Ca2+. The increase in cytoplasmic Ca2+ concentration induced by AVP was preserved in medium containing the calcium channel blockers Mg2+ (Mg2+ 31.2 mmol/l; Ca2+ 1.3 mmol/l) or nifedipine (1 mumol/l). The potassium-evoked calcium signal was blocked by Mg2+ (31.2 mmol/l). We conclude that vasopressin induces a rapid rise in the cytoplasmic concentration of free calcium ions in corticotrophs. Vasopressin may mobilize calcium through mechanisms that neither are glucocorticoid-sensitive nor involve the influx of extracellular calcium through voltage-dependent calcium channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

GRF elevates cytosolic free calcium concentration in rat anterior pituitary cells.

The effect of human growth hormone-releasing factor (GRF) on intracellular free calcium concentration ([Ca2+]i) was examined in rat anterior pituitary cells. The [Ca2+]i was monitored directly by means of the intracellularly trapped fluorescent indicator, fura-2. GRF rapidly elevated [Ca2+]i, reaching a new plateau within approximately 30 s. The half-maximally effective concentration of GRF was approximately 130 pM. GRF produced a maximal increase in [Ca2+]i by approximately 120 nM. The GRF (2 nM)-induced elevation of [Ca2+]i was abolished by removal of extracellular calcium (Ca2+ omitted, 2 mM EGTA). The GRF (2 nM)-caused rise in [Ca2+]i was largely reduced in the presence of the calcium channel blockers Mg2+ (31.2 mM) or nifedipine (1 microM). An increase in [Ca2+]i by approximately 60 nM was elicited by the addition of prostaglandin E2 (1 microM), which can stimulate growth hormone secretion independent of GRF receptors. These data indicate that GRF elevates the [Ca2+]i, possibly in somatotrophs; this GRF-induced increase in [Ca2+]i may depend on an influx of extracellular Ca2+, largely through Mg2+- and nifedipine-sensitive calcium channels.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMedDate not supplied

cAMP- and diacylglycerol-mediated pathways elevate cytosolic free calcium concentration via dihydropyridine-sensitive, omega-conotoxin-insensitive calcium channels in normal rat anterior pituitary cells.

The effect of 8-bromocyclic AMP (8-Br-cAMP) and phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, on cytosolic free calcium concentration ([Ca2+]i) in normal rat anterior pituitary cells was examined. [Ca2+]i was monitored directly by the fluorescent indicator fura-2. 8-Br-cAMP as well as PMA elevated [Ca2+]i in a concentration-dependent manner. Forskolin (10 mumol/l), which activates adenylate cyclase, and 1-oleoyl-2-acetyl-glycerol (10 mumol/l), another activator of protein kinase C, also increased [Ca2+]i. Both the 8-Br-cAMP (2 mmol/l)- and the PMA (100 nmol/l)-induced increase in [Ca2+]i was dependent on the presence of extracellular calcium and could be inhibited by the calcium channel blockers Mg2+ and nifedipine, but not by omega-conotoxin (100 nmol/l). The half-maximally inhibitory concentrations of Mg2+ and nifedipine were about 12 mmol/l and 160 nmol/l, respectively, for the [Ca2+]i response to 8-Br-cAMP (2 mmol/l), and were about 6 mmol/l and 400 nmol/l, respectively, for the PMA (100 nmol/l)-induced increase in [Ca2+]i. The sodium channel blocker tetrodotoxin (5 mumol/l) or PMA (100 nmol/l) on [Ca2+]i. After pretreatment for 3 min with PMA (100 nmol/l), the subsequent K+ (100 mmol/l)- or arachidonic acid (3 mumol/l)-induced increase in [Ca2+]i was decreased by about 50%. By contrast, pretreatment (3 min) with 8-Br-cAMP (2-10 mmol/l) markedly enhanced the subsequent [Ca2+]i response to K+ (100 mmol/l), and left the effect of arachidonic acid (3 mumol/l) on [Ca2+]i unimpaired.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗