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Biomedical subjects

E K Lee

Publications and source records attributed to E K Lee.

At least 19 recordsLinked to original sources
PubMed2001

Identification of a C-terminal region that regulates mitogen-activated protein kinase kinase-1 cytoplasmic localization and ERK activation.

The C-terminal region of mitogen-activated protein kinase kinase-1 and 2 (MKK1 and MKK2) may function in regulating interactions with upstream kinases or the magnitude and duration of ERK mitogen-activated protein kinase activity. The MKK C-terminal region contains a proline-rich region that reportedly functions in regulating interactions with the Raf-1 kinase and ERK activity. In addition, phosphorylation sites in the C terminus of MKK1 have been suggested to either sustain or attenuate MKK1 activity. To further understand how phosphorylation at the C terminus of MKK1 and protein interactions regulate MKK1 function, we have generated several MKK1 C-terminal deletion mutants and examined their function in regulating MKK1 localization, ERK protein activation, and cell growth. A deletion of C-terminal amino acids encompassing two putative alpha-helices between residues 330 and 379 caused a re-distribution of mutant MKK1 proteins to membrane compartments. Immunofluorescence analysis of MKK1 mutants revealed a loss of homogenous cytosolic distribution that is typically observed with MKK1 wild type, suggesting this region regulates MKK1 cellular localization. In contrast, MKK1 C-terminal deletion mutants localized to various sized punctate regions that overlapped with lysosome compartments. ERK activation in response to constitutively active Raf-1 or growth factor stimulus was attenuated in cells expressing MKK1 C-terminal deletion mutants. This could be partly explained by the inability of Raf-1 to phosphorylate MKK1 C-terminal deletion mutants even though the phosphorylation sites were intact in these mutants. Finally, we show that cells expressing MKK1 C-terminal deletion mutants displayed characteristic patterns of apoptotic cell death and reduced cell proliferation. These findings identify a novel C-terminal region between amino acid residues 330 and 379 on MKK1 that is necessary for regulating the cytoplasmic distribution and subsequent ERK protein activation necessary for cell survival and viability.

Base Sequence↗
PubMed2001

Lyapunov instability of rigid diatomic molecules in three dimensions.

We study the Lyapunov instability of a three-dimensional fluid composed of rigid diatomic molecules by molecular dynamics simulation. We use center-of-mass coordinates and angular variables for the configurational space variables. The spectra of Lyapunov exponents are obtained for 32 rigid diatomic molecules interacting through the Weeks-Chandler-Andersen potential for various bond lengths and densities. We show the general trends and characteristic features of the spectra of the Lyapunov exponents, and discuss the different contributions between translational and rotational degrees of freedom depending on the density and the bond length from the calculation of the projection of a certain subspace of the tangent space vectors.

Journal Article↗
PubMed2001

Multiple ligand interaction of alpha-synuclein produced various forms of protein aggregates in the presence of Abeta25-35, copper, and eosin.

Various protein aggregates of alpha-synuclein developed by way of the common protein self-oligomerization in the presence of Abeta25-35, copper, and eosin were examined. All the aggregates exhibited congo red birefringence although the actual amounts of the aggregates were varied as determined by thioflavin T binding fluorescence. When their morphologies were analyzed in relation to in vitro cytotoxicity, the smallest granular aggregates obtained with copper exhibited the highest cytotoxicity, while the fibrous structures by eosin did not affect the cell.

Amyloid beta-Peptides↗
PubMed2001

On the determination of an effective planning volume for permanent prostate implants.

PURPOSE: In current practice, planning for prostate brachytherapy is based on the state of the prostate at a particular instant in time. Because treatment occurs over an extended period, changes in the prostate volume (gland shrinkage) and seed displacement lead to disagreement between planned dosimetry to the prostate and the dose actually received by the prostate. Discrepancies between planned and actual dose to the rectum and urethra also occur. The purpose of this study is to investigate the possibility of defining an "effective planning volume" that compensates for changes in prostate volume and seed displacement. METHODS AND MATERIALS: Waterman's formula is used to estimate prostate shrinkage and seed displacement. The prostate volume and potential seed positions at days 0, 6, 12, 18, 24, and 30 are used in formulating time-dependent dosimetric treatment planning models. Both single-period and multi-period models are proposed and analyzed. A state-of-the-art computational engine generates unbiased, high-quality treatment plans in a matter of minutes. Plans are evaluated using coverage and conformity indices computed at specific times over a period of 30 days. The models allow dose to urethra and rectum to be strictly controlled at specific instants in time, or throughout the 30-day horizon. RESULTS: For plans generated from the single-period models-based on projected prostate volumes and potential seed positions on days t = 0, 6, 12, 18, 24, 30, respectively-as t increases, the conformity index improves while the coverage worsens. In particular, the best coverage and worst conformity are achieved for the plan generated using t = 0 (day 0) information. This plan provides over 99% coverage over the entire 30-day period, and while it has initial conformity index 1.24, the conformity index climbs to 1.58 by day 30. Conversely, the worst coverage and best conformity are achieved when the plan is generated using projected information from t = 30 (day 30). Plans based on projected data at day 30 yield an initial coverage of only 84%, with conformity scores less than 1.34 over the entire 30-day period. Among the multi-period plans, with the exception of the two-period plan obtained using day 0 and projected day 6 data, the average coverage is 98% while conformity indices below 1.46 are maintained throughout the 30-day horizon. Excessive dose to the urethra and rectum is observed when only day 0 dosimetric and volumetric data are imposed in the planning procedure. In this case, by day 30, 89% of urethra volume receives dose in excess of 120% of the remaining prescription dose. Similarly, 40% of rectum volume receives dose in excess of the prescribed upper dose bound of 78% of the remaining prescription dose. When multi-period dosimetric constraints for urethra and rectum are imposed, dose to these structures is controlled throughout the 30-day period. CONCLUSIONS: A planning method that takes into account prostate shrinkage and seed displacement over time can be used to adjust the balance between coverage and conformity. Incorporating projected future volumetric information is useful in providing more conformal plans, in some cases improving conformity by as much as 21% while sacrificing roughly 7% of initial coverage. Evidence of possible morbidity reduction to urethra and rectum via the use of multi-period dosimetric constraints on these structures is demonstrated. Among all plans considered, the plan obtained via the six-period model provides the best coverage and conformity over the 30-day horizon.

Brachytherapy↗
PubMed2001

Effect of potential energy distribution on the melting of clusters.

We find that the potential energy distribution of atoms in clusters can consistently explain many important phenomena related to the phase changes of clusters, such as the nonmonotonic variation of melting temperature with size, the dependence of melting, boiling, and sublimation temperatures on the interatomic potentials, the existence of a surface-melted phase, and the absence of a premelting peak in heat capacity curves. We also find a new type of premelting mechanism in double icosahedral Pd19 clusters, where one of the two internal atoms escapes to the surface at the premelting temperature.

Journal Article↗
PubMed2001

Refolding of protein inclusion bodies directly from E. coli homogenate using expanded bed adsorption chromatography.

To avoid the intrinsic problem of aggregation associated with the traditional solution-phase refolding process, we proposed a solid-phase refolding method integrated with the expanded bed adsorption chromatography. The model protein was a fusion protein of recombinant human growth hormone and a glutathione S-transferase fragment. It was demonstrated that the inclusion body proteins in the cell homogenate could be directly refolded with higher yield. To verify the applicability of this method, we have tested with success three types of the starting materials, i.e., rhGH monomer, inclusion bodies containing the fusion protein, and the E. coli cell homogenate. This direct refolding process could reduce the number of the renaturation steps required and allow the refolding at a higher concentration, approximately 2 mg fusion protein per ml resin.

Chromatography↗
PubMed2001

Self-oligomerization and protein aggregation of alpha-synuclein in the presence of Coomassie Brilliant Blue.

alpha-Synuclein has been implicated in various neurodegenerative disorders, including Parkinson's and Alzheimer's diseases, by its participation in abnormal protein depositions. As the protein has been suggested to play a significant role in the formation of the deposits which might be responsible for neurodegeneration, there is a strong demand to screen for alpha-synuclein-interactive small molecules. In this report, Coomassie Brilliant Blue (CBB) interaction of alpha-synuclein has been investigated with respect to induction of protein self-oligomerization in the presence of the chemical coupling reagent N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline. Both CBB-G and CBB-R, which differ by only two methyl groups, induced the self-oligomerization of alpha-synuclein in a biphasic manner with optimal dye concentrations of 250 microM and 150 microM, respectively. The protein aggregates of alpha-synuclein induced by the dyes in the absence of the coupling reagent were analysed by electron microscopy. Whereas CBB-G induced formation of protein aggregates with a worm-like structure, CBB-R induced clear fibrilization of alpha-synuclein on a background of granular structures. CBB-R interacted with alpha-synuclein approximately twice as effectively as CBB-G (dissociation constants 0.63 microM and 1.37 microM, respectively). These dye interactions were independent from the acidic C-terminus of alpha-synuclein, which was reminiscent of the Alphabeta25-35 interaction of alpha-synuclein. However, the metal-catalysed oxidative self-oligomerization of alpha-synuclein in the presence of Cu2+/H2O2, which was augmented synergistically by Alphabeta25-35, was not affected by the dyes. This indicates that the dye binding site is also distinctive from the Alphabeta25-35 interaction site on alpha-synuclein. These biochemically specific interactions between alpha-synuclein and the dyes indicate that alpha-synuclein-interactive small molecules could provide a tool with which to approach development of diagnostic, preventive, or therapeutic strategies for various alpha-synuclein-related neurodegenerative disorders.

Binding Sites↗
PubMed2001

A case of spontaneous pneumomediastinum and pneumopericardium in a young adult.

Spontaneous medialstinal emphysema (pneumomediastinum) and pneumopericardium may be defined as the presence of free air or gas in the mediastinal structures and in the pericardial sac without an apparent precipitating cause. It most frequently occurs in young healthy adults without serious underlying pulmonary disease. Although pneumomediastinum and pneumopericardium is often asymptomatic, it may cause pain in the neck and chest, dysphonia and shortness of breath. Treatment is supportive unless the patient has a history of trauma from foreign body aspiration. The course of spontaneous pneumomediastinum and pneumopericardium is usually benign and self-limited. A case of spontaneous pneumomediastinum, pneumopericardium and subcutaneous emphysema in a 20-year-old male is reported in this paper.

Adult↗
PubMed2001

Incidence of pulmonary tuberculosis in Korean civil servants: second study, 1992-1994.

SETTING: A survey based on biennial medical examinations for civil servants, including school teachers. OBJECTIVE: To estimate the incidence of pulmonary tuberculosis (PTB) for the general population from a sample survey, and to compare it with the previous results from 1988-1990. DESIGN: A retrospective follow-up study which started in April 1996 and ended in December 1997. Development of PTB among all South Korean civil servants who were tuberculosis-free in the 1992 biennial medical examination was followed up to the 1994 medical examination. The survey was based on newly-developed cases by 1) the findings of the biennial medical examination, 2) scrutiny of the medical records of all those claiming health insurance for tuberculosis, and 3) checking of the TB registers in all health centres during the period. Civil servants constituted 2.6% of the Korean population aged 20 to 64. RESULTS: Of 958137 subjects who were found to be TB-free in the 1992 medical examination, 957216 were eligible for the study. Radiologically active PTB was found in 4146 cases over the 2-year period of the study. Bacteriological examinations were performed in 3306 patients: there were 1551 bacteriologically proven cases (46.9%), including 1049 smear-positives (31.7%) and 502 smear-negative culture-positives (15.2%). The age-sex adjusted incidence rate for the general population was 202/100000 in radiologically active PTB, 81/100000 in bacteriologically proven PTB, and 54/100000 in smear-positive PTB. Overall PTB incidence rates were higher in males (240/100000) than in females (163/100000), and in the age group 20-24 years (280/ 100 000) than in the other age groups. CONCLUSION: Comparing the 1992-1994 PTB incidence with that observed in the 1988-1990 survey, the highest incidence was observed among young adults in both surveys, and it had not changed over time.

Adult↗
PubMed2000

Eosin interaction of alpha-synuclein leading to protein self-oligomerization.

Among various dyes including congo red, thioflavin S, thioflavin T, eosin, rhodamine 6G, and phenol red, the eosin was the only dye that induced self-oligomerization of alpha-synuclein in the presence of a chemical coupling reagent of N-(ethoxycarbonyl)-2-ethoxy-1, 2-dihydroquinoline. To analyze chemical nature of the eosin interaction with alpha-synuclein, the phenomenon of self-oligomerization was further examined with eosin congeners such as ethyl eosin, eosin B, phloxine B, erythrosin B, and rose bengal. The followings are the conclusions we have reached. First of all, intactness of the benzoate moiety of eosin and the negative charge on the carboxylic group of the dye are important factors leading to the specific interaction with alpha-synuclein. Secondly, the localized negative charge on the xanthene moiety of eosin is another critical factor for the interaction. As far as substituting halides are concerned, bromides and iodides on the xanthene moiety of the dyes do not make any difference on the alpha-synuclein interaction because both eosin and erythrosin B have induced the common phenomenon of self-oligomerization. The binding curve between eosin and alpha-synuclein was sigmoidal as the dye concentrations were increased. A double reciprocal plot of the saturation curve showed that the maximum number of eosin binding sites on alpha-synuclein was 1.85 with a dissociation constant of 390 microM. The dye binding to the protein appeared to occur via a positive cooperativity. The eosin binding site(s) was suggested to be located predominantly on the NAC region and partly related to the acidic C-terminus of alpha-synuclein. It has been, therefore, expected that this information might be useful to develop alpha-synuclein interactive molecules, which could provide eventual preventive or possible therapeutic means against various alpha-synuclein related disorders including Parkinson's disease.

Dose-Response Relationship, Drug↗
PubMed2000

Treatment planning for prostate implants using magnetic-resonance spectroscopy imaging.

PURPOSE: Recent studies have demonstrated that magnetic-resonance spectroscopic imaging (MRSI) of the prostate may effectively distinguish between regions of cancer and normal prostatic epithelium. This diagnostic imaging tool takes advantage of the increased choline plus creatine versus citrate ratio found in malignant compared to normal prostate tissue. The purpose of this study is to describe a novel brachytherapy treatment-planning optimization module using an integer programming technique that will utilize biologic-based optimization. A method is described that registers MRSI to intraoperative-obtained ultrasound images and incorporates this information into a treatment-planning system to achieve dose escalation to intraprostatic tumor deposits. METHODS: MRSI was obtained for a patient with Gleason 7 clinically localized prostate cancer. The ratios of choline plus creatine to citrate for the prostate were analyzed, and regions of high risk for malignant cells were identified. The ratios representing peaks on the MR spectrum were calculated on a spatial grid covering the prostate tissue. A procedure for mapping points of interest from the MRSI to the ultrasound images is described. An integer-programming technique is described as an optimization module to determine optimal seed distribution for permanent interstitial implantation. MRSI data are incorporated into the treatment-planning system to test the feasibility of dose escalation to positive voxels with relative sparing of surrounding normal tissues. The resultant tumor control probability (TCP) is estimated and compared to TCP for standard brachytherapy-planned implantation. RESULTS: The proposed brachytherapy treatment-planning system is able to achieve a minimum dose of 120% of the 144 Gy prescription to the MRS positive voxels using (125)I seeds. The preset dose bounds of 100-150% to the prostate and 100-120% to the urethra were maintained. When compared to a standard plan without MRS-guided optimization, the estimated TCP for the MRS-optimized plan is superior. The enhanced TCP was more pronounced for smaller volumes of intraprostatic tumor deposits compared to estimated TCP values for larger lesions. CONCLUSIONS: Using this brachytherapy-optimization system, we could demonstrate the feasibility of MRS-optimized dose distributions for (125)I permanent prostate implants. Based on probability estimates of anticipated improved TCP, this approach may have an impact on the ability to safely escalate dose and potentially improve outcome for patients with organ-confined but aggressive prostatic cancers. The magnitude of the TCP enhancement, and therefore the risks of ignoring the MR data, appear to be more substantial when the tumor is well localized; however, the gain achievable in TCP may depend quite considerably on the MRS tumor-detection efficiency.

Algorithms↗
PubMed2000

Analysis of expressed sequence tags of Porphyra yezoensis.

Single direct partial sequencing of anonymous cDNA clones was performed to obtain genetic information on red algae Porphyra yezoensis of which genetic information is not available. This expressed sequence tags (EST) analysis revealed 81 clones (42%) had significant homologies to known genes in GenBank. Of these clones, eight are related to known algal genes, whereas above 90% of the EST clones were newly identified in algae. Putative functional categories of these clones showed that the most abundant genes were involved in stress and defense mechanisms and that the next abundant genes were associated with protein synthetic pathways.

DNA, Complementary↗
PubMed2000

Dosimetric and volumetric criteria for selecting a source activity and a source type ((125)I or (103)Pd) in the presence of irregular seed placement in permanent prostate implants.

PURPOSE: The dosimetric merit of a permanent prostate implant relies on two factors: the quality of the plan itself, and the fidelity of its implementation. The former factor depends on source type and on source strength, while the latter is a combination of skill and experience. The purpose of this study is to offer criteria by which to select a source type ((125)I or (103)Pd) and activity. METHODS AND MATERIALS: Given a prescription dose and potential seed positions along needles, treatment plans were designed for a number of seed types and activities, specifically for (125)I with activities ranging from 0.3 to 0.7 mCi, and for (103)Pd with activities in the range of 0.8 to 1.6 mCi. To avoid human planner bias, an automated computerized planning system based on integer programming was used to obtain optimal seed configurations for each seed type and activity. To simulate the effect of seed-placement inaccuracies, random seed-displacement "errors" were generated for all plans. The displacement errors were assumed to be uniformly distributed within a cube with side equal to 2sigma. The resulting treatment plans were assessed using two volumetric and two dosimetric indices. RESULTS: For (125)I implants a coverage index (CI) of 98.5% or higher can be achieved for all activities (CI is the fraction of the target volume receiving the prescribed or larger dose). The external volume index (EI) (i.e., the amount of healthy tissue, as percentage of the target volume, receiving the prescribed or larger dose) increases from 13.9% to 20% as the activity increases from 0.3 to 0.7 mCi. For implants using (103)Pd, the external volume index increases from 10. 2% to 13.9% whenever CI exceeds 98.5%. Volumetric and dosimetric indices (coverage index, external volume index, D90, and D80) are all sensitive to seed displacement, although the activity dependence of these indices is more pronounced for (125)I than for (103)Pd implants. CONCLUSIONS: For both isotopes, the lower activities studied systematically result in lower EIs. If seeds can be placed within approximately 0.5 cm of their intended position (103)Pd should be preferred because its EI is lower than that of (125)I. For all activities the coverage indices and D90 are within the required range. If seed placement uncertainties are larger than 0.5 cm, (125)I provides slightly better target coverage; however, in terms of external volume (healthy tissue) covered, (103)Pd is superior to (125)I.

Brachytherapy↗
PubMed2000

Conditional expression of a Gi-coupled receptor causes ventricular conduction delay and a lethal cardiomyopathy.

Cardiomyopathy is a major cause of morbidity and mortality. Ventricular conduction delay, as shown by prolonged deflections in the electrocardiogram caused by delayed ventricular contraction (wide QRS complex), is a common feature of cardiomyopathy and is associated with a poor prognosis. Although the G(i)-signaling pathway is up-regulated in certain cardiomyopathies, previous studies suggested this up-regulation was compensatory rather than a potential cause of the disease. Using the tetracycline transactivator system and a modified G(i)-coupled receptor (Ro1), we provide evidence that increased G(i) signaling in mice can result in a lethal cardiomyopathy associated with a wide QRS complex arrhythmia. Induced expression of Ro1 in adult mice resulted in a >90% mortality rate at 16 wk, whereas suppression of Ro1 expression after 8 wk protected mice from further mortality and allowed partial improvement in systolic function. Results of DNA-array analysis of over 6,000 genes from hearts expressing Ro1 are consistent with hyperactive G(i) signaling. DNA-array analysis also identified known markers of cardiomyopathy and hundreds of previously unknown potential diagnostic markers and therapeutic targets for this syndrome. Our system allows cardiomyopathy to be induced and reversed in adult mice, providing an unprecedented opportunity to dissect the role of G(i) signaling in causing cardiac pathology.

Animals↗
PubMed2000

Scale-up process for expression and renaturation of recombinant human epidermal growth factor from Escherichia coli inclusion bodies.

A cDNA encoding mature epidermal growth factor (EGF) was isolated and cloned into a pQE30 vector in which the His(6)-tagged EGF was expressed. pH-stat feeding of concentrated medium at the time of isopropyl beta-D-thiogalactoside induction and slug-feedings of the enriched medium during the induction resulted in a higher cell density and specific expression. Using a simple refolding protocol that consisted of 1 mM L-cysteine addition for a 1-h reduction followed by 5 mM L-cystine addition for oxidative refolding, we were able to convert nearly all EGF monomers into the oxidized form. Also, there folding aggregate was converted into the monomeric form. Approx. 50% overall yield was obtained from the dissolved inclusion bodies to a single peak under FPLC. We hope that the result of this study may provide information that is useful for the scale-up of the recombinant human EGF production process.

Cell Division↗
PubMed2000

Norepinephrine regulation of growth hormone release from goldfish pituitary cells. I. Involvement of alpha2 adrenoreceptor and interactions with dopamine and salmon gonadotropin-releasing hormone.

Adrenergic regulation of growth hormone (GH) release in the goldfish was examined in vitro using dispersed goldfish pituitary cells under column perifusion. Norepinephrine and epinephrine suppressed basal GH release from goldfish pituitary cells in a reversible and dose-dependent manner. At high doses, a transient rebound of GH release was observed after termination of norepinephrine and epinephrine treatment. In this study, the dose-dependence of adrenergic inhibition on basal GH release was mimicked by the alpha2 agonists clonidine and UK14304. Basal GH secretion, however, was not affected by the beta agonist isoproterenol and alpha1 agonist methoxamine. In addition, the inhibitory actions of norepinephrine and clonidine on basal GH release were blocked by the alpha2 antagonists yohimbine and RX821002. The beta antagonist propranolol and alpha1 antagonists prasozin and benoxathian were not effective in this respect. Salmon gonadotropin-releasing hormone (sGnRH) and dopamine, two known GH-releasing factors in fish, stimulated GH release from goldfish pituitary cells and their GH-releasing actions were inhibited by simultaneous treatment with norepinephrine. Furthermore, the GH rebound after norepinephrine treatment was significantly enhanced by prior exposure to sGnRH and this effect was not observed with dopamine treatment. These results, taken together, suggest that in the goldfish adrenergic input at the pituitary level inhibit basal GH release through activation of alpha2 adrenoreceptors. This alpha2 inhibitory influence may interact with dopaminergic and GnRH input to regulate GH secretion from goldfish pituitary cells. The 'post-inhibition' GH rebound after NE treatment and its sensitivity to sGnRH potentiation may also represent a novel mechanism for GH regulation in fish.

Adrenergic Antagonists↗
PubMed2000

Norepinephrine regulation of growth hormone release from goldfish pituitary cells. II. Intracellular sites of action.

Previous results suggest that norepinephrine decreases growth hormone (GH) release in goldfish by means of alpha-2 adrenoceptor activation. The intracellular mechanisms by which norepinephrine inhibits GH release were examined in the present study using dispersed goldfish pituitary cells. In 2-h static incubation experiments, norepinephrine and the alpha-2 agonist clonidine decreased basal GH release and the GH responses to stimulation by the dopamine D1 agonist SKF38393 and two native gonadotropin-releasing hormones (GnRH). Norepinephrine also reduced GH responses to the adenylate cyclase activator forskolin, two protein kinase C (PKC) activators (phorbol ester and synthetic diacylglycerol), and two Ca2+ ionophores (ionomycin and A23187). Similarly, norepinephrine applied as a 1-h pulse in cell column perifusion experiments reduced basal GH release and abolished the GH response to a 5-min pulse of arachidonic acid. In goldfish, D1-stimulated GH release is mediated by AC-, arachidonic acid-and Ca2+-dependent pathways, whereas GnRH action is coupled to PKC-and Ca2+-dependent mechanisms. These results suggest that norepinephrine activation of alpha-2 receptors inhibits ligand-induced GH secretion by actions subsequent to activation of these second messenger cascades. To further characterize norepinephrine mechanisms of action on unstimulated hormone release, the ability of norepinephrine and an alpha-2 agonist to affect activation of two second messenger cascades under basal conditions was also investigated. Static incubation with clonidine reduced cAMP production in a time-and dose-dependent manner, suggesting that norepinephrine inhibitory action can also be expressed at the level of cAMP production. Resting intracellular free calcium levels in single, identified goldfish somatotropes was unaffected by norepinephrine. However, the inhibitory effects of norepinephrine on basal GH secretion was not observed in the presence of a voltage-sensitive Ca2+ channel agonist. Whether these channels are targets for norepinephrine action on unstimulated GH release requires further investigation.

Animals↗