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At least 1,621 records · Page 90Linked to original sources
PubMed2006

Genistein modulates the effects of parathyroid hormone in human osteoblastic SaOS-2 cells.

Genistein and parathyroid hormone (PTH) are anabolic agents that stimulate bone formation through their direct actions in osteoblastic cells. In the present study, we aimed to determine whether genistein modulates the actions of PTH in human osteoblastic SaOS-2 cells in an oestrogen-depleted condition. The present results showed that genistein (10(-8) to 10(-6) m) induced alkaline phosphatase (ALP) activity and osteoprotegrin (OPG) expression in SaOS-2 cells in a dose-dependent manner. These effects could be completely abolished by co-treatment with oestrogen antagonist ICI 182780 (7alpha-[9-[(4,4,5,5,5-pentafluoropentyl)sulfonyl]nonyl]-estra-1,3,5(10)-triene-3,17beta-diol). Genistein (at 1 microM) could stimulate the mRNA expression of receptor activator of NF-kappaB ligand (RANKL). As OPG and RANKL are known to modulate osteoclastogenesis, the ability of genistein to modulate OPG and RANKL expression in SaOS-2 cells suggested that it might modulate osteoclastogenesis through its direct actions on osteoblastic cells. PTH (at 10 nM) stimulated ALP activity, induced RANKL mRNA expression and suppressed OPG mRNA expression in SaOS-2 cells, confirming its bi-directional effects on osteoblastic cells. Pre-treatment of SaOS-2 cells with genistein and oestrogen not only enhanced PTH-induced ALP activity, but also attenuated PTH up regulation of RANKL mRNA expression and PTH down regulation of OPG mRNA expression. Taken together, the present study provides the first evidence that genistein could modulate the actions of PTH in human osteoblastic SaOS-2 cells in an oestrogen-depleted condition.

Alkaline Phosphatase↗
PubMed1993

Control of Equilibrium Position and Stiffness Through Postural Modules.

If muscles are viewed as spring-like torque generators, then the integral of torque with respect to joint angle is the potential energy of that muscle. An energy function for the musculoskeletal system can be defined by summing the energy contribution of each muscle and the potential energy stored in the limb. Any local minimum in this energy landscape is a possible equilibrium position for the limb. The gradient of this function with respect to joint angles is a torque field, and the task of postural control is to find a set of muscle activations to produce a desired field. We consider one technique by which this approximation may be achieved: A postural module is defined as a synergy of muscles that produce a class of torque functions that converge at a constant equilibrium position, but whose stiffness at this position varies as a function of activation of the postural module. For a single-joint system, we show that through control of two such modules it is possible to produce any stiffness at any desired equilibrium position. To extend this scheme to a multijoint system, we initially derive the mechanical constraints on the shape of the restoring force field when a multijoint limb is displaced from equilibrium. Next, we consider voluntary control of the force field when the human arm is displaced from equilibrium: Mussa-Ivaldi, Hogan, and Bizzi (1985) have suggested that subjects are unable to voluntarily change the shape and orientation of the field, although they can readily scale it. This suggests existence of a limitation on the independent recruitment of arm muscles. We show, through simulation, that the inability to voluntarily control the shape and orientation of the restoring force field can be attributed to an organization of postural modules that act as local stiffness controllers. We propose that through coactivation, postural modules coarsely encode the work space and serve as an intermediate control system in the motor control hierarchy.

Journal Article↗
PubMedDate not supplied

Transthoracic defibrillation with chopping-modulated biphasic waveforms.

The superiority of different biphasic pulses for transthoracic defibrillation was proven by several studies. These efficient waveforms were implemented in some commercially available defibrillators. Recently we have devised and evaluated a biphasic waveform with a specially balanced ratio of the first-to-second phase voltages and with 5 kHz frequency 1:1 on-off chopping. It used less than half the energy for successful defibrillation in comparison with the 'classic' monophasic damped sinusoidal wave and showed considerably less post-shock negative effects. This experience led us to try several laws of chopping modulation. A pulse-width modulation, combining low energy with gradual upslope of the modelled transmembrane potential, proved to have better performance than the standard damped sinusoid wave and the non-chopped biphasic truncated exponential pulse. This waveform was tested in a series of animal experiments in comparison with other modulated pulses, with the non-modulated waveform and the standard damped sinusoid wave. The experiments demonstrated the superiority of the modulated waveform, assessed by combining the parameters of threshold defibrillation energy and of post-shock disturbances reduction.

Animals↗
PubMed2000

A computer-based epidemiological skills module for medical undergraduates in Nepal.

OBJECTIVE: To ascertain whether undergraduate medical students could acquire the basic competence needed to design, analyze and use a computer-compatible database in an epidemiologically meaningful way. SETTING: Since 1998 the Manipal College of Medical Sciences (MCOMS) of Kathmandu University (KU), Nepal has included in its undergraduate medical curriculum a training module that incorporates knowledge and skills in doing computer-assisted data analyses of epidemiological questions. The present study was designed around the implementation of this module. SUBJECTS: All 96 students of the seventh semester (first six months of the fourth year) of the MBBS course at the MCOMS. METHODS: The teaching-learning activities for the module were carried out mainly in six 2-hour sessions, for groups of 16 students at a time. The software used was EPI-INFO. MAIN OUTCOME MEASURES: Knowledge and skills of computer-assisted data analyses were assessed. In addition, feedback was obtained from the students and scored on seven dimensions. FINDINGS: The pre-test/post-test questionnaire score difference, which evaluated the knowledge component, was highly significant (t = 51.3, p < 0.001). In the skills assessment session, 83% were successful. The students gave high average scores on the satisfaction, small group learning environment, curricular relevance and evaluation dimensions; but the scores were relatively low on the time, other resources and confidence dimensions. CONCLUSION: The module was successful in achieving its objectives and can be implemented even under tight resource constraints. Our plans for improving upon this first run of the module are outlined in the paper.

Journal Article↗
PubMed2004

Near-threshold recordings of amplitude modulation following responses (AMFR) in children of different ages.

Amplitude modulation following responses (AMFR) to single near-threshold 40-Hz or 80-Hz amplitude-modulated tones of 1 kHz were recorded in 48 normal children between the ages of 2 months and 14 years. Children under the age of 2 years were tested during natural sleep, and older children were tested awake. The objectives of this study were to find out how the AMFR changes with age and to determine the most effective modulation frequency for objective threshold assessment at different ages. The optimal modulation frequency changed from higher to lower modulation frequencies at about 13 years. In younger children, the 80-Hz AMFR was larger than the 40-Hz AMFR. The 40-Hz response became similar to the adult response by the age of 14 years, while the 80-Hz response had an amplitude greater than half of an adult response by the age of 1 year, changed very little during the investigated period, and reached the amplitude of adult responses at the end of the investigated period.

Adolescent↗
PubMed2004

Herbal modulation of P-glycoprotein.

P-glycoprotein (Pgp) is a 170 kDa phosphorylated glycoprotein encoded by human MDR1 gene. It is responsible for the systemic disposition of numerous structurally and pharmacologically unrelated lipophilic and amphipathic drugs, carcinogens, toxins, and other xenobiotics in many organs, such as the intestine, liver, kidney, and brain. Like cytochrome P450s (CYP3A4), Pgp is vulnerable to inhibition, activation, or induction by herbal constituents. This was demonstrated by using an ATPase assay, purified Pgp protein or intact Pgp-expressing cells, and proper probe substrates and inhibitors. Curcumin, ginsenosides, piperine, some catechins from green tea, and silymarin from milk thistle were found to be inhibitors of Pgp, while some catechins from green tea increased Pgp-mediated drug transport by heterotropic allosteric mechanism, and St. John's wort induced the intestinal expression of Pgp in vitro and in vivo. Some components (e.g., bergamottin and quercetin) from grapefruit juice were reported to modulate Pgp activity. Many of these herbal constituents, in particular flavonoids, were reported to modulate Pgp by directly interacting with the vicinal ATP-binding site, the steroid-binding site, or the substrate-binding site. Some herbal constituents (e.g., hyperforin and kava) were shown to activate pregnane X receptor, an orphan nuclear receptor acting as a key regulator of MDR1 and many other genes. The inhibition of Pgp by herbal constituents may provide a novel approach for reversing multidrug resistance in tumor cells, whereas the stimulation of Pgp expression or activity has implication for chemoprotective enhancement by herbal medicines. Certain natural flavonols (e.g., kaempferol, quercetin, and galangin) are potent stimulators of the Pgp-mediated efflux of 7,12-dimethylbenz(a)-anthracene (a carcinogen). The modulation of Pgp activity and expression by these herb constituents may result in altered absorption and bioavailability of drugs that are Pgp substrates. This is exemplified by increased oral bioavailability of phenytoin and rifampin by piperine and decreased bioavailability of indinavir, tacrolimus, cyclosporine, digoxin, and fexofenadine by coadministered St. John's wort. However, many of these drugs are also substrates of CYP3A4. Thus, the modulation of intestinal Pgp and CYP3A4 represents an important mechanism for many clinically important herb-drug interactions. Further studies are needed to explore the relative role of Pgp and CYP3A4 modulation by herbs and the mechanism for the interplay of these two important proteins in herb-drug interactions.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Laminin alpha3 LG4 module induces keratinocyte migration: involvement of matrix metalloproteinase-9.

Laminin alpha3 chain, a functionally key subunit of laminin-5, contains a large globular module (G module) which consists of a tandem repeat of five homologous LG modules (LG1-5). We previously demonstrated that the LG4 module of laminin alpha3 chain (alpha3 LG4) induces a matrix metalloproteinase-1 (MMP-1) expression through the interaction with syndecans leading to MAPK activation/IL-1beta expression signaling loop (Utani et al., J. Biol. Chem. 278, 34483-34490, 2003). Here, we show that a recombinant alpha3 LG4 and synthetic peptides containing syndecan binding motif induced a cell motility and a MMP-9 expression in ketarinocytes. The synthetic peptide (A3G756)-induced cell migration and MMP-9 upregulation were inhibited by each application of a heparin and an IL-1 receptor antagonist (IL-1RA), suggesting the involvement of syndecans and IL-1beta autocrine. Furthermore, the A3G756-induced cell motility was inhibited by an MMP-9 inhibitor and a neutralizing antibody of MMP-9, indicating induced cell motility was dependent on an MMP-9 activity. Taken these together, laminin-5 alpha3 LG4 module may play an important role in re-epithelialization at tissue remodeling.

Amino Acid Sequence↗
PubMed1977

Antigenic modulation of Friend virus erythroleukemic cells in vitro by serum from mice with dormant erythroleukemia.

Friend leukemia virus (FLV) erythroleukemic cells cultured in medium containing FLV-immune serum from dormant FLV-infected mice undergo modulation of FLV cell surface antigens. Modulation was determined by an increased resistance to FLV antibody-mediated complement-dependent lysis and was associated temporally with the capping of FLV-immune complexes at the cell surface. Modulated cells regained their susceptibility to FLV antibody-mediated complement-dependent lysis when transferred to medium containing normal mouse serum. After 48 h of culture in FLV-immune serum, 26% of the FLV erythroleukemic cells were devoid of FLV cell surface antigens as demonstrated by immunofluoresence. Antigenic modulation occurred to a greater extent in cells maintained in logarithmic growth than in cells in GO or resting phase. FLV-antigenic modulation is discussed as a possible mechanism by which antibody induces and maintains FLV-transformed cells in a dormant state.

Animals↗
PubMed1987

Antibody-induced modulation of the CD3/T cell receptor complex causes T cell refractoriness by inhibiting the early metabolic steps involved in T cell activation.

We investigated the mechanism involved in T cell unresponsiveness that follows the monoclonal antibody-induced surface modulation of the CD3-TCR complex. We determined whether modulation of CD3-TCR affected the early metabolic steps such as [Ca2+]i rise and InsP3 formation. A strong inhibition of the increase on [Ca2+]i mediated by either anti-TCR or anti-CD2 mAbs was detected. In contrast, surface modulation of CD2 molecules did not prevent the [Ca2+]i increase induced by anti-TCR mAb. Similarly, InsP3 increase was strongly reduced only after modulation of CD3-TCR complex (but not of CD2 molecules). Therefore, it appears that surface modulation of CD3-TCR complex causes T cell refractoriness by inhibiting the very early metabolic events that follow receptor-ligand interactions.

Antibodies, Monoclonal↗
PubMed1997

Calcium modulation of ligand affinity in the cyclic GMP-gated ion channels of cone photoreceptors.

To investigate modulation of the activation of cGMP-gated ion channels in cone photoreceptors, we measured currents in membrane patches detached from the outer segments of single cones isolated from striped bass retina. The sensitivity of these channels to activation by cGMP depends on the history of exposure to divalent cations of the membrane's cytoplasmic surface. In patches maintained in 20 microM Ca++ and 100 microM Mg++ after excision, the current amplitude dependence on cGMP is well described by a Hill equation with average values of K1/2, the concentration necessary to activate half the maximal current, of 86 microM and a cooperativity index, n, of 2.57. Exposing the patch to a solution free of divalent cations irreversibly increases the cGMP sensitivity; the average value of K1/2 shifts to 58.8 microM and n shifts to 1.8. Changes in cGMP sensitivity do not affect other functional parameters of the ion channels, such as the interaction and permeation of mono- and divalent cations. Modulation of cGMP activation depends on the action of an endogenous factor that progressively dissociates from the channel as Ca++ concentration is lowered below 1 microM. The activity of the endogenous modulator is not well mimicked by exogenously added calmodulin, although this protein competes with the endogenous modulator for a common binding site. Thus, the modulation of cGMP affinity in cones depends on the activity of an unidentified molecule that may not be calmodulin.

Ambystoma↗
PubMed2000

Ion-Ion interactions at the selectivity filter. Evidence from K(+)-dependent modulation of tetraethylammonium efficacy in Kv2.1 potassium channels.

In the Kv2.1 potassium channel, binding of K(+) to a high-affinity site associated with the selectivity filter modulates channel sensitivity to external TEA. In channels carrying Na(+) current, K(+) interacts with the TEA modulation site at concentrations </=30 microM. In this paper, we further characterized the TEA modulation site and examined how varying K(+) occupancy of the pore influenced the interaction of K(+) with this site. In the presence of high internal and external [K(+)], TEA blocked 100% of current with an IC(50) of 1.9 +/- 0.2 mM. In the absence of a substitute permeating ion, such as Na(+), reducing access of K(+) to the pore resulted in a reduction of TEA efficacy, but produced little or no change in TEA potency (under conditions in which maximal block by TEA was just 32%, the IC(50) for block was 2.0 +/- 0.6 mM). The all-or-none nature of TEA block (channels were either completely sensitive or completely insensitive), indicated that one selectivity filter binding site must be occupied for TEA sensitivity, and that one selectivity filter binding site is not involved in modulating TEA sensitivity. At three different levels of K(+) occupancy, achieved by manipulating access of internal K(+) to the pore, elevation of external [K(+)] shifted channels from a TEA-insensitive to -sensitive state with an EC(50) of approximately 10 mM. Combined with previous results, these data demonstrate that the TEA modulation site has a high affinity for K(+) when only one K(+) is in the pore and a low affinity for K(+) when the pore is already occupied by K(+). These results indicate that ion-ion interactions occur at the selectivity filter. These results also suggest that the selectivity filter is the site of at least one low affinity modulatory effect of external K(+), and that the selectivity filter K(+) binding sites are not functionally interchangeable.

Amino Acid Substitution↗
PubMed1998

Scanned intensity modulations for 50 MV photons.

Optimization of the dose distributions by individual beam compensation is a useful tool in conformal radiation therapy. Intensity modulation by electromagnetic scanning of a narrow elementary beam allows fast dose delivery and causes little change in beam quality compared with other methods, especially for high energies such as 50 MV. Intensity modulated beams from the MM50 accelerator were measured and compared with calculations based on Monte Carlo simulations. Good agreement between measurements and calculations were found, typically within 1% for central dose profiles. The steepest wedge angle that was produced with the scanning beam technique was of 45 degrees or 3.5% cm(-1) for a 20 cm x 20 cm field, slightly varying with depth. The elementary 50 MV photon 'pencil beam' for a full range, high-z bremsstrahlung target, is a wide dose distribution at 10 cm depth in water which limits the modulation gradient and hence the complexity of the modulation by the scanning of a photon pencil beam only. Scanned wedge beam distributions were modelled in the treatment planning system and a pelvic treatment with three fields was used to illustrate a clinical application. The resulting dose volume data were compared for different radiation qualities but with similar beam portals. 'Energy modulation' by field matching with lower photon energies was performed to sharpen the penumbra towards organs at risk.

Electromagnetic Fields↗
PubMed1999

Intensity modulation methods for proton radiotherapy.

The characteristic Bragg peak of protons or heavy ions provides a good localization of dose in three dimensions. Through their ability to deliver laterally and distally shaped homogenous fields, protons have been shown to be a precise and practical method for delivering highly conformal radiotherapy. However, in an analogous manner to intensity modulation for photons, protons can be used to construct dose distributions through the application of many individually inhomogeneous fields, but with the localization of dose in the Bragg peak providing the possibility of modulating intensity within each field in two or three dimensions. We describe four different methods of intensity modulation for protons and describe how these have been implemented in an existing proton planning system. As a preliminary evaluation of the efficacy of these methods, each has been applied to an example case using a variety of field combinations. Dose-volume histogram analysis of the resulting dose distributions shows that when large numbers of fields are used, all techniques exhibit both good target homogeneity and sparing of neighbouring critical structures, with little difference between the four techniques being discerned. As the number of fields is decreased, however, only a full 3D modulation of individual Bragg peaks can preserve both target coverage and sparing of normal tissues. We conclude that the 3D method provides the greatest flexibility for constructing conformal doses in challenging situations, but that when large numbers of beam ports are available, little advantage may be gained from the additional modulation of intensity in depth.

Computing Methodologies↗
PubMed2002

Optimization of intensity-modulated very high energy (50-250 MeV) electron therapy.

This work evaluates the potential of very high energy (50-250 MeV) electron beams for dose conformation and identifies those variables that influence optimized dose distributions for this modality. Intensity-modulated plans for a prostate cancer model were optimized as a function of the importance factors, beam energy and number of energy bins, number of beams, and the beam orientations. A trial-and-error-derived constellation of importance factors for target and sensitive structures to achieve good conformal dose distributions was 500, 50, 10 and I for the target, rectum, bladder and normal tissues respectively. Electron energies greater than 100 MeV were found to be desirable for intensity-modulated very high energy electron therapy (VHEET) of prostate cancer. Plans generated for lower energy beams had relatively poor conformal dose distributions about the target region and delivered high doses to sensitive structures. Fixed angle beam treatments utilizing a large number of fields in the range 9-21 provided acceptable plans. Using more than 21 beams at fixed gantry angles had an insignificant effect on target coverage, but resulted in an increased dose to sensitive structures and an increased normal tissue integral dose. Minor improvements in VHEET plans utilizing a 'small' number (< or =9) of beams may be achieved if, in addition to intensity modulation, energy modulation is implemented using a small number (< or =3) of beam energies separated by 50 to 100 MeV. Rotation therapy provided better target dose homogeneity but unfortunately resulted in increased rectal dose, bladder dose and normal tissue integral dose relative to the 21-field fixed angle treatment plan. Modulation of the beam energy for rotation therapy had no beneficial consequences on the optimized dose distributions. Lastly, selection of beam orientations influenced the optimized treatment plan even when a large number of beams (approximately 15) were employed.

Electrons↗
PubMed2003

Intensity modulated radiation therapy using laser-accelerated protons: a Monte Carlo dosimetric study.

In this paper we present Monte Carlo studies of intensity modulated radiation therapy using laser-accelerated proton beams. Laser-accelerated protons coming out of a solid high-density target have broad energy and angular spectra leading to dose distributions that cannot be directly used for therapeutic applications. Through the introduction of a spectrometer-like particle selection system that delivers small pencil beams of protons with desired energy spectra it is feasible to use laser-accelerated protons for intensity modulated radiotherapy. The method presented in this paper is a three-dimensional modulation in which the proton energy spectrum and intensity of each individual beamlet are modulated to yield a homogeneous dose in both the longitudinal and lateral directions. As an evaluation of the efficacy of this method, it has been applied to two prostate cases using a variety of beam arrangements. We have performed a comparison study between intensity modulated photon plans and those for laser-accelerated protons. For identical beam arrangements and the same optimization parameters, proton plans exhibit superior coverage of the target and sparing of neighbouring critical structures. Dose-volume histogram analysis of the resulting dose distributions shows up to 50% reduction of dose to the critical structures. As the number of fields is decreased, the proton modality exhibits a better preservation of the optimization requirements on the target and critical structures. It is shown that for a two-beam arrangement (parallel-opposed) it is possible to achieve both superior target coverage with 5% dose inhomogeneity within the target and excellent sparing of surrounding tissue.

Algorithms↗
PubMed2004

Analysis of stochastic noise in intensity-modulated beams.

Inverse planning techniques are known to produce intensity-modulated beams (IMBs) that are highly modulated. They are characterized by the fact that they contain high-frequency modulations that are absent in the profiles that are easier to deliver. For the purpose of this study these clinically unwanted fluctuations are being defined as 'noise'. Although these highly modulated solutions are also optimal solutions, as soon as the profiles are being delivered, they become unfavourable with respect to delivery efficiency and the analysis and verification of treatment. The aim of this work was therefore to understand the origins of the structure and complexity of IMBs. Ultimately, if one can characterize the essential features in optimum beam profiles, it might be possible to control the frequency distribution of IMBs and simplify the IMRT planning and delivery process. The study was based on two common optimization techniques: simulated annealing (SA) and gradient-descent (GD). The assumptions made at the start of this work were that the stochastic noise caused by the SA optimization technique is dominant over other sources of noise and that it could be separated out from the essential modulation after convergence of the cost function by averaging minimum-cost fluence profiles. The results indicate that there are three possible sources of stochastic noise in IMBs, i.e. the optimization technique, the cost function and the definition of convergence of that cost function. In terms of the optimization technique itself, it was confirmed that the gradient-descent technique does not introduce stochastic noise in the IMBs. The SA technique does introduce stochastic noise but averaging of minimum-cost fluence profiles does not result in smoother beam profiles. This originates from the fact that this type of noise is not the dominant factor in the optimization, but rather the curvature of the cost function close to the global minimum. It is shown that the choice of initial temperature in the SA optimization technique is crucial for the convergence of the cost function and the frequency distribution of the fluence profiles. If the initial temperature is too small the stochastic noise will get frozen into the fluence profiles and become the dominant component of noise, resulting in very random-looking and difficult to deliver patterns.

Algorithms↗
PubMed2004

Performance measurements of a depth-encoding PET detector module based on position-sensitive avalanche photodiode read-out.

We are developing a high-resolution, high-efficiency positron emission tomography (PET) detector module with depth of interaction (DOI) capability based on a lutetium oxyorthosilicate (LSO) scintillator array coupled at both ends to position-sensitive avalanche photodiodes (PSAPDs). In this paper we present the DOI resolution, energy resolution and timing resolution results for complete detector modules. The detector module consists of a 7 x 7 matrix of LSO scintillator crystals (1 x 1 x 20 mm3 in dimension) coupled to 8 x 8 mm2 PSAPDs at both ends. Flood histograms were acquired and used to generate crystal look-up tables. The DOI resolution was measured for individual crystals within the array by using the ratio of the signal amplitudes from the two PSAPDs on an event-by-event basis. A measure of the total scintillation light produced was obtained by summing the signal amplitudes from the two PSAPDs. This summed signal was used to measure the energy resolution. The DOI resolution was measured to be 3-4 mm FWHM irrespective of the position of the crystal within the array, or the interaction location along the length of the crystal. The total light signal and energy resolution was almost independent of the depth of interaction. The measured energy resolution averaged 14% FWHM. The coincidence timing resolution measured using a pair of identical detector modules was 4.5 ns FWHM. These results are consistent with the design goals and the performance required of a compact, high-resolution and high-efficiency PET detector module for small animal and breast imaging applications.

Equipment Design↗
PubMed1994

Modulation of intraocular pressure by adenosine agonists.

Adenosine receptors have been shown to modulate a variety of physiological functions; however, little is known about the role these receptors play in the modulation of ocular function. To investigate the potential role of adenosine receptors in modulating intraocular pressure (IOP), the A1 agonist N6-cyclopentyladenosine (CPA), the nonselective adenosine agonist 5'-N-ethylcarboxamideadenosine (NECA) and the A2 agonist 8-phenylaminoadenosine (CV-1808) were evaluated. Topical administration of NECA produced a dose-related reduction in IOP. However, an initial ocular hypertension of 1 to 2 hours was also observed in rabbits treated with NECA. The administration of CPA (165 micrograms) resulted only in a reduction in IOP, while the administration of CV-1808 produced only an initial ocular hypertension. As adenosine A1 receptors have been shown to be negatively coupled to adenylate cyclase in several systems, CPA was evaluated for its ability to suppress cAMP formation in the isolated iris/ciliary body. CPA produced a dose-related suppression of cAMP accumulation induced by 10(-6) M forskolin (EC50 = 3.2 nM). These results indicate that selected adenosine agonists can modulate IOP. The ocular hypotension induced by adenosine agonists is consistent with the activation of adenosine A1 receptors and may involve the modulation of cAMP levels in the iris/ciliary body.

Adenosine↗