Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Caffeine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources
PubMedDate not supplied

Effects of caffeine on locomotor activity of horses: determination of the no-effect threshold.

Caffeine is the legal stimulant consumed most extensively by the human world population and may be found eventually in the urine and/or blood of race horses. The fact that caffeine is in foods led us to determine the highest no-effect dose (HNED) of caffeine on the spontaneous locomotor activity of horses and then to quantify this substance in urine until it disappeared. We built two behavioural stalls equipped with juxtaposed photoelectric sensors that emit infrared beams that divide the stall into nine sectors in a 'tic-tac-toe' fashion. Each time a beam was interrupted by a leg of the horse, a pulse was generated; the pulses were counted at 5-min intervals and stored by a microcomputer. Environmental effects were minimized by installing exhaust fans producing white noise that obscured outside sounds. One-way observation windows prevented the animals from seeing outside. The sensors were turned on 45 min before drug administration (saline control or caffeine). The animals were observed for up to 8 h after i.v. administration of 2.0, 2.5, 3.0 or 5.0 mg caffeine kg(-1). The HNED of caffeine for stimulation of the spontaneous locomotor activity of horses was 2.0 mg kg(-1). The quantification of caffeine in urine and plasma samples was done by gradient HPLC with UV detection. The no-effect threshold should not be greater than 2.0 microg caffeine ml(-1) plasma or 5.0 microg caffeine ml(-1) urine.

Animals↗
PubMed1993

Inhibition of induced endochondral bone development in caffeine-treated rats.

We have addressed questions raised by the observation in fetal rats of delayed ossification induced by caffeine at maternal doses above 80 mg/kg body weight per day. The effect of caffeine on endochondral bone development and mineralization has been studied in an experimental model system of bone formation which involves implantation of demineralized bone particles (DBP) in subcutaneous pockets of young growing rats. Caffeine's effects on cellular events associated with endochondral ossification were examined directly by quantitating cellular mRNA levels of chondrocyte and osteoblast growth and differentiation markers in DBP implants from caffeine-treated rats harvested at specific stages of development (day 7 through day 15). Oral caffeine administration to rats implanted with DBP resulted in a dose dependent inhibition of the formation of cartilage tissue in the implants. Histologic examination of the implants revealed a decrease in the number of cells which were transformed to chondrocytes compared to control implants. Those cartilaginous areas that did form, however, proceeded through the normal sequelae of calcified cartilage and bone formation. At the 100 mg/kg dose, cellular levels of mRNA for histone, collagen type II, and TGF beta were all reduced by greater than 40% of control implants consistent with the histological findings. Alkaline phosphatase activity in the implants and mRNA levels for proteins reflecting the hypertrophic chondrocyte and bone phenotype, collagen type I and osteocalcin were markedly decreased compared to controls. Lower doses of 50 and 12.5 mg/kg caffeine also resulted in decreased cellular proliferation and transformation to cartilage histologically and reflected by significant inhibition of type II collagen mRNA levels (day 7). The effects of caffeine on gene expression observed in vivo during the period of bone formation (day 11 to day 15) in the DBP model were similar to the inhibited expression of H4, alkaline phosphatase, osteocalcin, and osteopontin found in fetal rat calvarial derived osteoblast cultures following 24 hour exposure of the cultures to 0.4 mM caffeine. Thus the observed delayed mineralization in the fetal skeleton associated with caffeine appears to be related to an inhibition of endochondral bone formation at the early stages of proliferation of undifferentiated mesenchymal cells to cartilage specific cells as well as at later stages of bone formation.

Administration, Oral↗
PubMed2003

Caffeine induces G2/M arrest and apoptosis via a novel p53-dependent pathway in NB4 promyelocytic leukemia cells.

Methylxantine derivative, caffeine, is known to prevent the p53-dependent apoptosis pathway via inhibition of ATM (ataxia telangiectasia mutated) kinase, which activates p53 by phosphorylation of the Ser-15 residue. In contrast, it has been reported that caffeine induces p53-mediated apoptosis through Bax protein in non-small-cell lung cancer cells. Therefore, the effects of caffeine on cellular growth in malignant cells are controversial. We investigated the effects of caffeine on cell proliferation, cell cycle progression, and induction of apoptosis in NB4 promyelocytic leukemia cells containing wild-type p53. Caffeine suppressed the cellular growth of NB4 cells in a dose- and time-dependent manner. Caffeine induced G(2)/M phase cell cycle arrest in NB4 cells in association with the induction of phosphorylation at the Ser-15 residue of p53 and induction of tyrosine phosphorylation of cdc2. Expression of Bax protein was increased in NB4 cells after treatment with caffeine. Interestingly, the antisense oligonucleotides for p53 significantly reduced p53 expression and caffeine-induced G(2)/M phase cell cycle arrest in NB4 cells. These results suggest that caffeine induces cell cycle arrest and apoptosis in association with activation of p53 by a novel pathway to phosphorylate the Ser-15 residue and induction of phosphorylation of cdc 2 in leukemic cells with normal p53.

Apoptosis↗
PubMed1994

Separate effects of caffeine and dbcAMP on macaque sperm motility and interaction with the zona pellucida.

Capacitation of macaque sperm with caffeine and dbcAMP is required for fertilization in vitro. This study determined the separate effects of caffeine and dbcAMP on sperm-zona pellucida binding and the acrosome reaction of zona bound sperm. Semen from 6 cynomolgus macaques was washed through 60% Percoll, resuspended, and washed with BWW media and incubated for 2.5 hr. Caffeine, dbcAMP (2 mM each), or both (1 mM each) were added to aliquots of the sperm suspensions. Immature macaque oocytes were placed into drops of sperm suspensions, coincubated with sperm for 30 sec, and either fixed immediately or removed to sperm-free media and incubated 1 hr before fixation. There were no significant differences between groups in the percentage of live, acrosome-reacted sperm in suspension. Treatment with caffeine and dbcAMP or with caffeine alone, significantly increased the number of sperm bound to each zona pellucida (96 +/- 16 and 81 +/- 17, respectively) compared to control and dbcAMP treatment (15 +/- 4 and 28 +/- 13). However, treatment with dbcAMP, alone and with caffeine, resulted in a higher percentage of acrosome-reacted sperm on the zona (15.2 +/- 2.1 and 9.0 +/- 0.6) than control or caffeine treatment (3.0 +/- 1.4 and 2.4 +/- 0.5). Effects on sperm motility consistent with hyperactivation were detected only when both caffeine and dbcAMP were present. Although both caffeine and dbcAMP are presumed to increase or to produce the same effect as increased intracellular cAMP levels, these compounds have different effects on the ability of sperm to bind to the zona and to undergo the acrosome reaction.

Acrosome↗
PubMed1995

Imaging of caffeine-inducible release of intracellular calcium in cultured embryonic mouse telencephalic neurons.

To gain a better understanding of Ca(2+)-induced Ca2+ release in central neurons, we have studied the increase in intracellular Ca2+ concentration ([Ca2+]i) induced by application of caffeine to cells cultured from embryonic mouse telencephalon (hippocampus or cortex). The magnitudes and distributions of changes in [Ca2+]i in neuron somata were measured by quantitative video microscopy. We observed that application of caffeine to pyramidally shaped neurons typically initiated an increase in [Ca2+]i in the cytoplasmic region between the nucleus and the base of a major dendrite. [Ca2+] in this region increased over a period of 3 to 6 s and was followed by, with a slight delay, a surge of Ca2+ that moved across the soma and into or over the nucleus. Similar Ca2+ responses to caffeine were observed in Ca(2+)-containing and nominally Ca(2+)-free external solutions, suggesting that caffeine was inducing Ca2+ release from intracellular stores. Ca2+ responses to caffeine were potentiated by inducing a tonic Ca2+ influx through N-methyl-D-aspartate (NMDA)-type glutamate receptors activated by 0.3 microM glutamate and multiple responses to caffeine could be elicited by using this Ca2+ influx to refill the intracellular stores. Ryanodine inhibition of caffeine-induced Ca2+ release was use- and concentration-dependent; the median effective concentration EC50 for ryanodine declined from 22 microM for the first application of caffeine to 20 nM for the fourth. We conclude, based on these responses to caffeine, that ryanodine-sensitive mechanisms of intracellular Ca2+ release are active in hippocampal and cortical neurons and may be involved in generation of directed Ca2+ waves that engulf the nucleus.

Animals↗
PubMed1992

Caffeine potentiates airway responsiveness in the neonatal lamb.

In contrast to its effect on airway smooth muscle in the adult, in vitro studies have shown that caffeine significantly increases active tension in airway smooth muscle in the neonatal lamb. To determine if caffeine has a physiological effect on airway function during early development, we studied the effect of caffeine on acetylcholine-induced bronchoconstriction in two groups of neonatal lambs. The animals were anesthetized, paralyzed, and maintained normoxic and normocapnic with mechanical ventilation. Pulmonary mechanics were evaluated as indices of airway tone, and functional residual capacity was used as an index of lung volume; heart rate and mean arterial pressure were used to assess cardiovascular status. Acetylcholine-induced bronchoconstriction was evaluated as percentage changes of airway conductance and lung compliance from baseline, before and 1 hour after administration of normal saline or caffeine, and it was further analyzed with respect to the dose that produced a 20% change in those values (PD20). There were no significant alterations in baseline lung mechanics, lung volume, or mean arterial pressure following saline or caffeine infusion. However, caffeine produced a left shift in the acetylcholine dose-response curve for conductance and compliance and a significant decrease (-52%; P less than 0.001) in PD20 for conductance. There were no significant alterations in any parameter following saline administration. Since caffeine is used commonly for the treatment of apnea of prematurity, it is noteworthy that caffeine increases airway reactivity at clinically relevant doses. These findings raise important issues regarding the use of caffeine for the treatment of apnea of prematurity.

Acetylcholine↗
PubMed2001

Interactions in developmental toxicology: combined action of restraint stress, caffeine, and aspirin in pregnant mice.

BACKGROUND: Stress can result in an increased use of substances such as caffeine and aspirin. The effect of maternal stress on concurrent exposure to caffeine and aspirin on prenatal development was assessed in mice. METHODS: On gestational day 9, mice were assigned to three treatment groups orally exposed to caffeine (30 mg/kg), aspirin (250 mg/kg), or a combination of caffeine (30 mg/kg) and aspirin (250 mg/kg). Three additional groups of pregnant animals received similar caffeine and aspirin doses and were immediately subjected to restraint for 14 hr. Control groups included unrestrained and restrained pregnant mice not exposed to caffeine or aspirin. All dams were euthanized on gestational day 18. Live fetuses were evaluated for sex, body weight, and external, internal, and skeletal malformations and variations. RESULTS: A single oral dose of caffeine or aspirin did not cause significant maternal toxicity. However, coadministration of these drugs with restraint produced some adverse maternal effects (i.e., reduction in maternal weight gain and food consumption on gestational days 9-11). In relation to embryo/fetal toxicity, the incidence of some skeletal defects was significantly increased after exposure to caffeine, aspirin, or maternal restraint, and their binary and ternary combinations. CONCLUSIONS: Although caffeine and aspirin were given in a single dose in this study, the results suggest that prenatal stress could slightly exacerbate the maternal and developmental toxicity of the combination of these drugs in mice.

Abnormalities, Drug-Induced↗
PubMed1985

Developmental and cytogenetic effects of caffeine on mouse blastocysts, alone or in combination with benzo(a)pyrene.

Mouse blastocysts were treated with caffeine and/or benzo(a)pyrene (BP), and the effects on development and on induction of sister chromatid exchanges (SCEs) were examined. Caffeine interfered with blastocyst development in a dose-related manner. At 4 mM, the highest concentration tested, caffeine interfered with development of blastocysts to all four endpoints: hatching, trophoblast outgrowth, inner cell mass (ICM) growth, and two-layer (primary endoderm and ectoderm) differentiation of ICMs. At 2 mM, caffeine reduced the incidence of both ICM growth and differentiation but did not affect hatching or formation of trophoblast outgrowths. At 1 mM, caffeine interfered only with ICM differentiation. Cell proliferation was least sensitive to caffeine and was reduced at concentrations of greater than or equal to 2 mM. Induction of SCEs was most sensitive to caffeine exposure; an increase in SCE frequency was observed at 0.1 and 0.5 mM. When caffeine was added to cultures with BP (1 microM, a concentration that was not embryotoxic and did not induce SCEs), both embryotoxic effects and SCE frequency were increased. The enhancing effect on SCE induction was particularly marked; as little as 0.1 mM caffeine was sufficient to cause doubling of induced SCE frequencies when added to cultures with BP.

Animals↗
PubMed2000

Orientation of caffeine within the active site of human cytochrome P450 1A2 based on NMR longitudinal (T1) relaxation measurements.

Longitudinal (T1) relaxation studies were performed in order to examine the interaction of caffeine with the heme of human P450 1A2. Addition of caffeine to this P450 resulted in a small, incomplete conversion of the heme from high spin to low spin, as shown by changes in the optical spectrum. Determination of a relatively large dissociation constant (Ks = 2.6 mM) as well as the relative instability of the P450 after 2 h at room temperature necessitated the performance of these experiments at high concentrations (25 mM) of caffeine. The relaxation measurements on the three sets of methyl hydrogens led to the determination of the corresponding distances between the iron and the methyl groups on the bound caffeine as well as the position and orientation of caffeine within the active site of P450 1A2. The three methyl groups were found to be nearly equidistant from the iron (> or = 4.79-4.89 A), with slight preference for the N-3 position, and thus, the average position of caffeine was parallel to the heme. In vitro incubations with P450 1A2 and 5 mM caffeine led primarily to paraxanthine formation (N-3 demethylation), as expected. However, with 25 mM substrate, the overall extent of oxidation was doubled and there was more equivalent oxidation at each of the four potential sites on caffeine. This latter observation was consistent with the lack of selective positioning of the N-3 methyl group of caffeine relative to the heme.

Binding Sites↗
PubMed1998

Complications associated with rapid caffeine application to cardiac myocytes that are not voltage clamped.

The rapid application of caffeine to cardiac myocytes is commonly used to assess changes in the Ca2+ content of the sarcoplasmic reticulum (SR) and to study other parameters of intracellular Ca2+ regulation. Here we examined the effects of rapid caffeine application on membrane potential, intracellular Ca2+, and cell shortening in ventricular myocytes (rat, rabbit, guinea pig, dog) and atrial myocytes (rabbit) that were not voltage clamped. Conditioning pacing was used to achieve a steady-state level of SR Ca2+ loading prior to caffeine (10 mM) application. Caffeine transiently depolarized myocytes as expected from activation of forward Na+-Ca2+ exchange. However, we also found in each species (50% rat, 36% rabbit ventricular, 53% rabbit atrial, 56% guinea pig, 31% dog) that the caffeine-induced depolarization could also trigger an action potential. Caffeine-triggered potentials were completely blocked by thapsigargin (1 microM). The Ca2+ transient and contraction that accompanied caffeine-triggered action potentials had a larger magnitude and slower rate of decline (or relaxation) than occurred during caffeine-induced subthreshold depolarizations. Thus, the use of rapid caffeine application to study SR function and [Ca2+]i regulation in myocytes that are not voltage clamped can yield erroneous results.

Animals↗
PubMed1995

Caffeine enhances sympathetic purinergic and noradrenergic transmission in the guinea-pig isolated vas deferens.

Intracellular recording techniques were used to monitor the resting membrane potential of smooth muscle cells and the excitatory junction potentials (EJPs) evoked by stimulation of the hypogastric nerve. Stimulation with trains of 15 pulses at 1 Hz or 0.33 Hz evoked individual EJPs which increased in amplitude from the first pulse and reached a plateau after 6-8 pulses. Stimulation at 1 Hz resulted in EJPs facilitating to a plateau level of approximately 25 mV, whereas with stimulation at 0.33 Hz the EJPs only facilitated to a plateau level of about 12 mV. With stimulation at 1 Hz, caffeine (3 mM and 10 mM), increased the amplitude of the first few EJPs in each train and decreased the extent of facilitation and reduced the amplitude of fully facilitated EJPs. In comparison, the amplitude of all EJPs evoked by stimulation at 0.33 Hz was increased by caffeine (3 mM and 10 mM). With 0.33 Hz stimulation, facilitation of the first few EJPs was observed in the presence of 3 mM caffeine but not in the presence of 10 mM caffeine. In the presence of the alpha 2-adrenoceptor antagonist idazoxan, caffeine (3 mM and 10 mM) still enhanced the amplitude of EJPs early in trains of stimulation but there was no depression of EJPs later in the trains. Similarly, in reserpine-treated vasa deferentia, caffeine (3 mM) enhanced EJPs early in the train of stimulation at 1 Hz and there was no depression of EJPs at the end of the train. In addition to electrophysiological experiments, the effect of caffeine (0.1-30 mM) on the resting and stimulation-induced (S-I) efflux of radioactivity was investigated in guinea-pig isolated vasa deferentia previously incubated with [3H]-noradrenaline. Caffeine (10 mM) did not affect the resting efflux of [3H]-noradrenaline but significantly enhanced the S-I efflux by 150-160%. The present findings suggest that caffeine enhances sympathetic purinergic and noradrenergic transmission at the sympathetic neuroeffector junction in the guinea-pig vas deferens. Moreover, the increased release of transmitter noradrenaline can modulate purinergic transmission by activation of alpha 2-adrenoceptors located at sympathetic neuroeffector sites.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1988

Multiple effects of caffeine on contraction and cytosolic free Ca2+ levels in vascular smooth muscle of rat aorta.

1. Effects of caffeine on cytosolic Ca2+ level ([Ca2+]cyt), measured simultaneously with muscle tension using fura-2-Ca2+ fluorescence, were examined in isolated smooth muscle of rat aorta. 2. Caffeine (20 mmol/l) induced a large transient increase in [Ca2+]cyt followed by a plateau which was higher than resting level. However, muscle tension showed a transient increase followed by a decrease to or below the resting level. In Ca2+-free solution, caffeine induced only a transient increase in both [Ca2+]cyt and muscle tension. 3. At low temperature (22 degrees C), high K+ (72.7 mmol/l) induced sustained increase in both [Ca2+]cyt and muscle tension which were smaller than those observed at 37 degrees C. At 22 degrees C, however, caffeine-induced transient changes were greater than those observed at 37 degrees C. 4. Ryanodine (10 mumol/l) inhibited the transient changes due to caffeine but showed little effects on the sustained changes due to high K+. 5. During the sustained increase in [Ca2+]cyt induced by noradrenaline (10 mumol/l) or high K+ (140 mmol/l), addition of caffeine transiently increased [Ca2+]cyt followed by a decrease to a level slightly lower than that before the addition of caffeine. In contrast to this, muscle tension transiently increased and then decreased to or below the resting level. 6. These results suggest that caffeine-induced contraction is due to the release of Ca2+ from cellular store. Caffeine also has an inhibitory effect which is partly attributable to decrease in [Ca2+]cyt and partly to the decrease in the sensitivity to Ca2+ of the contractile elements.

Animals↗
PubMed1982

The effect of maternal caffeine ingestion on pancreatic function in the neonatal rat.

Pancreatic function was investigated in neonatal suckling offspring of caffeine-ingesting dams, with or without maternal sucrose supplementation, throughout pregnancy and lactation. In offspring of rats ingesting caffeine without sucrose supplementation, there was initial hyperinsulinaemia, followed by a progressive fall of plasma insulin to subnormal levels. This fall in plasma insulin coincided with depletion of pancreatic insulin stores. Both the fall in plasma insulin and depletion of pancreatic insulin stores were prevented by sucrose supplementation of caffeine-ingesting dams. Offspring of dams fed sucrose alone and control offspring also maintained pancreatic insulin stores and circulating insulin levels over the first 14 days of postnatal life. Pancreases from offspring of caffeine-exposed animals tested in vitro showed enhanced sensitivity of the insulin release process to glucose. This was reflected in the glucose concentration required to elicit half-maximal insulin release (2.4 +/- 0.2 mmol/l for caffeine offspring, 2.3 +/- 0.2 mmol/l for caffeine with sucrose, 3.8 +/- 0.3 mmol/l for sucrose and 4.1 +/- 0.3 mmol/l for control offspring, mean +/- SEM). In contrast, offspring of sucrose-supplemented (with or without caffeine) dams showed increased sensitivity of the proinsulin biosynthetic process to glucose, whereas offspring of dams ingesting caffeine alone showed no significant enhancement of the biosynthetic process compared with control offspring. Thus enhanced sensitivity of the insulin secretory process to glucose without a change in the sensitivity of the biosynthetic process in the offspring of the caffeine ingesting (non-sucrose supplemented) dams could explain the progressive depletion of pancreatic insulin stores and eventual hypoinsulinaemia seen in this group.

Animals↗
PubMed1992

Caffeine has the capacity to stimulate calcium release in organ culture of neonatal mouse calvaria.

In view of the possible association between ingestion of caffeine (a constituent of coffee, tea, and several beverages) and osteoporosis, we have studied the effect of caffeine on bone resorption in vitro. Caffeine caused a dose-dependent increase of the spontaneous release of 45Ca from neonatal mouse calvarial bones. The effect of caffeine was less pronounced than that of parathyroid hormone (PTH), but of the same magnitude as that of theophylline, a structurally related methylxanthine. The enhancement of 45Ca release induced by caffeine and PTH was observed in 5 days culture. In 2 days culture, however, only PTH stimulated mineral mobilization. The delayed stimulatory effect of caffeine in long-term cultures was abolished by indomethacin and flurbiprofen. In indomethacin-treated bones, however, caffeine potentiated the stimulatory effect on 45Ca release induced by choleratoxin and forskolin. In contrast, caffeine did not potentiate 45Ca release stimulated by PTH. These data show that caffeine can stimulate calcium release from bone in vitro and that this effect is due to potentiation of a stimulatory action of a bone resorptive agonist acting via the adenylate cyclase-cyclic AMP system.

Animals↗
PubMed1993

Modulation of sarcoplasmic reticulum Ca(2+)-release channels by caffeine, Ca2+, and Mg2+ in skinned myocardial fibers of fetal and adult rats.

Ryanodine causes depression of the caffeine-induced tension transient (ryanodine depression) in skinned muscle fibers, because it blocks the sarcoplasmic reticulum (SR) Ca(2+)-release channels [Su, J. Y. (1988) Pflügers Arch 411:132-136, 371-377; (1992) Pflügers Arch 421:1-6]. This study was performed to examine the sensitivity of SR Ca(2+)-release channels to ryanodine in fetal compared to adult myocardium and to investigate the influence of Ca2+, caffeine, and Mg2+ on ryanodine depression in skinned fibers. Ryanodine (0.3 nM-1 microM) caused a dose-dependent depression in skinned myocardial fibers of the rat, and the fetal fibers (IC50 approximately 74 nM) were 26-fold less sensitive than those of the adult (IC50 approximately 2.9 nM). The depression induced by 0.1 microM or 1 microM ryanodine was a function of [caffeine], or [Ca2+] (pCa < 6.0), which was potentiated by caffeine, and an inverse function of [Mg2+]. At pCa > 8.0 plus 25 mM caffeine, a 20% ryanodine depression was observed in both the fetal and adult fibers, indicating independence from Ca2+. Ryanodine depression in skinned fibers of the fetus was less affected than that seen in the adult by pCai, [caffeine]i, or 25 mM caffeine plus pCai or plus pMgi (IC50 approximately pCa 4.5 versus 5.1; caffeine 12.7 mM versus 2 mM; pCa 6.7 versus 7.3; and pMg 3.9 versus 3.3 respectively). The results show that the SR Ca(2+)-release channel in both fetal and adult myocardium is modulated by Ca2+, caffeine, and Mg2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of caffeine on intracellular calcium, calcium current and calcium-dependent potassium current in anterior pituitary GH3 cells.

Caffeine elicits physiological responses in a variety of cell types by triggering the mobilization of Ca2+ from intracellular organelles. Here we investigate the effects of caffeine on intracellular Ca2+ concentration ([Ca2+]i) and ionic currents in anterior pituitary cells (GH3) cells. Caffeine has a biphasic effect on Ca(2+)-activated K+ current [IK(Ca)]: it induces a transient increase superimposed upon a sustained inhibition. While the transient increase coincides with a rise in [Ca2+]i, the sustained inhibition of IK(Ca) is correlated with a sustained inhibition of the L-type Ca2+ current. The L-type Ca2+ current is also inhibited by other agents that mobilize intracellular Ca2+, including thyrotropin releasing hormone (TRH) and ryanodine, but in a matter distinct from caffeine. Unlike the caffeine effect, the TRH-induced inhibition "washes-out" under whole-cell patch-clamp conditions and is eliminated by intracellular Ca2+ chelators. Likewise, the ryanodine-induced inhibition desensitizes while the caffeine-induced inhibition does not. Simultaneous [Ca2+]i and Ca2+ current measurements show that caffeine can inhibit Ca2+ current without changing [Ca2+]i. Single-channel recordings show that caffeine reduces mean open time without affecting single-channel conductance of L-type channels. Hence the effects of caffeine on ion channels in GH3 cells are attributable both to mobilization of intracellular Ca2+ and to a direct effect on the gating of L-type Ca2+ channels.

Animals↗
PubMed1976

Effects of caffeine consumption on nicotine consumption.

Coffee-drinking cigarette smokers take in more nicotine when they ingest almost no caffeine than when they ingest an amount of caffeine ranging from 75 mg to 300 mg. They do not take in relatively less nicotine as the dose of caffeine increases from 75 mg to 300 mg. It seems, then, that something due to caffeine deficit is responsible for the effect. Heavier users of caffeine show this effect less strongly than do lighter users of caffeine. These results are discussed in terms of the discriminability of caffeine and nicotine deficits and the possible influence of differential tolerance to caffeine. The importance of evaluating caffeine consumption when studying nicotine use and the importance of considering the chronic level and use of these drugs when studying their effects on behavior is indicated.

Caffeine↗
PubMed1995

Expression of apoptosis-related oncoproteins and modulation of apoptosis by caffeine in human leukemic cells.

We investigated the modulation of radio- and chemoresistance by caffeine and mechanisms of resistance in human leukemic cell lines and mononuclear cells from 18 leukemic patients. Caffeine synergistically potentiated cytotoxicity and apoptosis induced by ionizing radiation or carboplatin (CPt), but attenuated induction of apoptosis by daunorubicin (DNR) in KG-1a cells. Since caffeine released irradiated as well as DNR-treated KG-1a cells from G2M cell cycle arrest and CPt-treated cells from S-phase arrest, this release does not fully explain the different effects of caffeine. Caffeine synergistically reduced the level of the apoptosis inhibitor glutathione after irradiation or CPt treatment. In contrast, treatment with DNR plus caffeine diminished glutathione levels to a lesser extent than DNR alone. We conclude that the effect of caffeine on glutathione depletion represents a mechanism of action by which caffeine can modulate apoptosis. Caffeine increased CPt cytotoxicity in K562 cells and its doxorubicin-resistant subline (K562/ADM), but little effect was seen in HL-60 cells or mononuclear cells from leukemic patients. Multivariate cluster analysis revealed an association of CPt resistance with the expression of c-Fos, c-N-Ras, and p53 oncoproteins and with proliferative activity (S-phase of cell cycle), but not with Bcl-2 expression.

Apoptosis↗