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Biomedical subjects

I Kojima

Publications and source records attributed to I Kojima.

At least 199 records · Page 11Linked to original sources
PubMed1985

Role of calcium and cAMP in the action of adrenocorticotropin on aldosterone secretion.

When the dose-response curve of adrenocorticotropin (ACTH)-induced aldosterone secretion is compared to that of ACTH-induced intracellular cAMP, the ED50 for intracellular cAMP is more than 10 times as high as that for aldosterone production. In contrast, the dose-response curve of forskolin-induced aldosterone secretion correlates well with that for forskolin-induced intracellular cAMP. ACTH, but not forskolin, increases calcium influx into glomerulosa cells without inducing the mobilization of calcium from an intracellular pool. The effect of ACTH on calcium influx is dose-dependent and ED50 is 3.5 X 10(-11) M. In a perifusion system, the effect of 1 nM ACTH on aldosterone secretion is much greater than that of 1 microM forskolin, even though these two stimulators induce identical increases in the intracellular cAMP. Perifusion with combined A23187 (50 nM) and forskolin (1 microM) stimulates aldosterone secretion to a value comparable to that induced by 1 nM ACTH. Likewise, BAY K 8644 (1 nM), which induces a comparable increase in calcium influx, potentiates the effect of 1 microM forskolin. When the intracellular [Ca2+] is fixed at either 100 or 300 nM, forskolin-stimulated intracellular cAMP content is identical, but ACTH-stimulated intracellular cAMP content at 100 nM [Ca2+]i is 60% of that at 300 nM [Ca2+]i. Both the ACTH- and forskolin-induced aldosterone secretion rate is higher at 300 nM than at 100 nM [Ca2+]i. These results indicate that ACTH stimulates calcium influx, that calcium potentiates ACTH-induced but not forskolin-induced cAMP generation, and that Ca2+ and cAMP act as synarchic messengers in ACTH-mediated aldosterone secretion.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Comparison of patterns of prolactin release in GH4C1 cells and primary pituitary cultures.

The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA, an activator of C-kinase), the cation ionophore A23187, forskolin (an activator of adenylate cyclase) and thyrotropin-releasing hormone (TRH) on prolactin release from anterior pituitary cells in primary culture were investigated and compared to the effects of these same agents on prolactin release from GH4C1 cells. In both GH4C1 cells and primary pituitary cultures, 100 nM TRH increased prolactin release 3- to 5-fold within 4 min after the stimulation started. This peak response was followed by a fall to a sustained increased rate of release approximately 1.5-fold above the basal rate. The decline after the early peak was slower in primary cultures than in GH4C1 cells. Addition of 20 microM A23187 to primary cultures caused a rapid 2- to 4-fold increase in release that fell to basal values within 12 min after the stimulation started. In GH4C1 cells, A23187 caused a rise in prolactin release of less than 2-fold that was sustained longer than the rise seen in primary cultures. Perifusion of either type of cells with 50 nM TPA caused a rapid 2- to 2.5-fold increase in release that also was sustained for 30 min or more in both types of cells. Perifusion with combined TPA and A23187 caused a 3- to 5-fold increase in rate of release from each cell type that declined rapidly to a 2-fold sustained release in primary cultures, and that declined more slowly in GH4C1 cells. Forskolin, 1 microM, had only a small effect by itself, but potentiated the effect of TPA or combined TPA and A23187 in both types of cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of ANG II and K+ on Ca efflux and aldosterone production in adrenal glomerulosa cells.

A comparison was made of the effects of angiotensin II (ANG II) and K+ on aldosterone secretion and calcium efflux from porcine adrenal glomerulosa cells. In the presence of 1.25 mM Ca2+ in the perifusion medium, both 1 x 10(-9) M ANG II and 12 mM K+ caused a 3-fold increase in rate of aldosterone secretion. ANG II caused a 3.5-fold increase in the fractional efflux ratios of radiocalcium from cells prelabeled with 45Ca, but K+ caused only a 1.5-fold increase. When the perifusate contained no Ca2+ or the Ca2+ was replaced by 0.6 mM Sr2+, the effects of K+ on both 45Ca efflux and aldosterone production were abolished. On the other hand, ANG II still caused approximately the same increase in the fractional efflux ratio of radiocalcium and 25-50% of the normal increase in aldosterone production rate. When the perifusate contained 1.25 mM calcium and 25 microM dantrolene, K+ produced the same 1.5-fold increase in calcium efflux and the same maximal rate of aldosterone production as seen in the absence of dantrolene. In contrast, dantrolene greatly inhibited ANG II-induced increase in the fractional efflux ratio of calcium, 1.5-fold compared with 3.5-fold in the absence of dantrolene. Likewise, dantrolene delayed the onset of the ANG II-induced increase in aldosterone secretion and reduced the maximal rate of secretion to 50%. Cells incubated with both dantrolene and media containing no Ca2+ or containing Sr2+ in place of Ca2+ showed no response to ANG II either in terms of calcium efflux or aldosterone production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1985

Possible role of phospholipase A2 action and arachidonic acid metabolism in angiotensin II-mediated aldosterone secretion.

When [3H]arachidonic acid-labeled calf adrenal glomerulosa cells are stimulated by angiotensin II (AII), free [3H]arachidonic acid is released. AII treatment significantly decreases radioactivity in phosphatidylinositol but not in other phospholipids. Inhibitors of phospholipase A2 (PL-A2) activity, quinacrine and p-bromophenacyl bromide, inhibit AII-stimulated aldosterone secretion from glomerulosa cells in a dose-dependent manner. The effect of these inhibitors is irreversible when used at high concentration, but not when employed at lower concentration. Exogenous PL-A2 as well as arachidonic acid stimulates both radiocalcium efflux and aldosterone secretion. Unlike AII, stimulation of aldosterone secretion by PL-A2 is only transient. Radiocalcium efflux induced by PL-A2 is greater than that induced by AII and is not inhibited by either nitrendipine or dantrolene. Pretreatment with PL-A2 abolishes the radiocalcium efflux response to subsequent AII, whereas AII pretreatment does not abolish the subsequent PL-A2-mediated radiocalcium efflux response. The aldosterone secretory response to AII is not affected by 0.3 microM indomethacin but is inhibited by either of three compounds which inhibit lipoxygenase activity; 5,8,11,14-eicosatetraynoic acid, BW755c, or caffeic acid. In a static incubation system, AII-stimulated aldosterone secretion is inhibited 40-50% by any of these lipoxygenase inhibitors. In a perifusion system, BW755c partially inhibits only the sustained phase of AII-stimulated aldosterone secretion. However, BW755c has no effect on the secretion of aldosterone in response to combined A23187 plus 12-O-tetradecanoyl-phorbol-13-acetate. These results suggest that PL-A2 action is not obligatory in AII-induced aldosterone secretion and that lipoxygenase, but not cyclooxygenase, products of arachidonic acid metabolism may play a role in AII action as positive feed forward mediators.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1985

Mutual relation of three pock-forming plasmids resident in Streptomyces noursei.

From Streptomyces noursei B3, two plasmids--designated pSCY5 and pSCY6--were isolated in addition to the known plasmid pSCY3. Strains carrying one or more of these plasmids generated pocks on a lawn of the plasmid-free strain, S. noursei KL3. The pocks elicited by pSCY3 and pSCY5 belonged to the A type; i.e., showed a clear inhibition zone, while those produced by pSCY6 were of the B type; i.e., exhibited a turbid inhibition zone. The strains carrying either pSCY3 or pSCY5, were also capable of forming pocks on a lawn of S. noursei 6T-11 harboring pSCY6, and vice versa. However, pock formation was not observed between strains harboring pSCY3 and strains carrying pSCY5. The endonuclease cleavage maps of these plasmids revealed that pSCY3 differed clearly from that of pSCY6, whereas pSCY5 was found to be a hybrid plasmid consisting of the entire pSCY3 plasmid and an 8.4 Md or longer fragment originating from pSCY6. The pocks elicited by pSCY5 were much smaller than those produced by pSCY3. Transformation experiments showed that pSCY6 elicited pocks in Streptomyces lividans as well as in S. noursei, whereas the pSCY6 transformants of S. lividans failed to produce pocks on a lawn of plasmid-free S. noursei.

Chromosome Mapping↗
PubMed1984

The temporal integration of the aldosterone secretory response to angiotensin occurs via two intracellular pathways.

Angiotensin II (AII) regulates the secretion of aldosterone from adrenal glomerulosa cells by a calcium-dependent mechanism which involves both the uptake of calcium from the extracellular pool, and the release of calcium from a dantrolene-sensitive intracellular pool. In the present study, it was shown that AII induces the rapid (10 s) hydrolysis of phosphatidylinositol 4-phosphate and -4,5-bisphosphate, leading to the sustained production of inositol bis- and trisphosphate (Ins-P3), and diacylglycerol rich in arachidonic acid. Saponin-permeabilized glomerulosa cells accumulate calcium into a nonmitochondrial pool by an ATP-dependent manner. Ins-P3 (0.5-5 microM) induces a release of Ca2+ from this pool. This release was blocked by dantrolene (10 microM). Adrenal glomerulosa cells were shown to contain the calcium-activated, phospholipid-dependent protein kinase (C-kinase). Perfusion of glomerulosa cells with combined 12-O-tetradecanoyl phorbol 13-acetate and A23187 induced an immediately developing, sustained, maximal secretory response similar to that induced by AII. These data are interpreted in terms of a model in which, after AII addition, there is a flow of information through two separate branches of the calcium messenger system, each with its unique temporal role: a calmodulin branch activated by the transient rise in the [Ca2+] in the cell cytosol, which is largely responsible for the initial transient cellular response; and a C-kinase branch activated by the increase in both cytosolic [Ca2+] and the diacylglycerol content of the plasma membrane, which is largely responsible for the sustained phase of the cellular response. The temporal integration of these two phases underlies the observed pattern of cellular response.

Adrenal Cortex↗
PubMed1984

Synergistic stimulation of prolactin release by phorbol ester, A23187 and forskolin.

The effects of 12-0-tetradecanoyl-phorbol-13-acetate (TPA), A23187, forskolin and thyrotropin-releasing hormone (TRH) on prolactin release from GH4C1 cells were compared. TPA caused a 2-fold release, maximum after 6 or more min, that was sustained for 30 min or more. A23187 caused only a small and variable response that peaked within 4 to 6 min. Combination of TPA and A23187 caused a rapid 3- to 5-fold increase in release that declined slowly. TRH increased prolactin release 3- to 5-fold, reaching a maximum within 4 min, followed by sustained release at lower rates. Forskolin had little effect by itself, but potentiated release caused either by combined TPA and A23187, or by TRH. These data are consistent with a model in which two branches of the Ca2+ messenger system participate in the action of TRH, a calmodulin branch and a C-kinase branch that interact to cause large amounts of sustained release. Forskolin, by regulating the cyclic AMP content of the cell determines the set point around which the Ca2+ messenger system operates.

Animals↗
PubMed1984

TPA-induced contraction of isolated rabbit vascular smooth muscle.

Myosin light chain phosphorylation may not regulate the sustained phase of vascular smooth muscle contraction. Another, unidentified, calcium-dependent pathway may be involved in this process. TPA, an activator of C-kinase, at concentrations of 10 to 333 nM induces a calcium-dependent contraction of vascular smooth muscle which develops slowly but progressively to reach values of 50-300 mm Hg. Arteries exposed to the ionophore A23187, in a calcium-free medium, display a uniform series of contractile responses when exposed to 1.5 mM Ca2+ for 2 min once every 10 min. Exposure to 100 nM TPA as well as ionophore leads to a progressive enhancement of these calcium-induced, contractile responses. Arteries stimulated by brief (10 sec), repetitive (every 3 min) electrical pulses, respond with a series of comparable phase 1 responses. Prior exposure of vessels to 10 nM TPA, causes a progressive increase in the magnitude of these responses to repetitive electrical stimulation. Addition of 25 microM forskolin, an activator of adenylate cyclase, to TPA-treated, partially-contracted muscle leads to the immediate inhibition of the TPA-induced contraction. These data suggest that the activation of C-kinase plays a significant role in regulating vascular smooth muscle contraction.

Animals↗
PubMed1984

Circulating digitalis-like substance is increased in DOCA-salt hypertension.

Blood pressure and digitalis-like substance were measured in the plasma of control, salt-treated, and DOCA-salt treated rats. Blood pressure in DOCA-salt treated rats was significantly higher than that of either control or salt-treated animals. Digitalis-like activity was measured by two methods, radioimmunoassay for digoxin, and a receptor binding assay employing a rat brain synaptosomal membrane fraction. Digoxin-like immunoreactivity in plasma was not detected in either control or salt-treated rats, but was detected in DOCA-salt treated rats. Receptor binding activity in salt-treated rats was slightly but significantly higher than that of control rats. In DOCA-salt treated rats, receptor binding activity was significantly higher than that of salt-treated rats. Partial purification of the digitalis-like substance in plasma was performed by gel filtration using Sephadex G-25. Two peaks containing digoxin-like immunoreactivity were observed. Receptor binding activity, as well as Na+-K+ ATPase inhibitory activity, was detected only in the second peak, in which approximately 70% of the digoxin-like immunoreactivity was eluted. These results indicate that a circulating digitalis-like substance is increased in DOCA-salt hypertension.

Animals↗
PubMed1984

Dihydropyridine calcium agonist and antagonist effects on aldosterone secretion.

The effects of the dihydropyridine calcium antagonists nimodipine, nitrendipine, and nisoldipine were studied on K+-induced and angiotensin II (ANG II)-induced aldosterone secretion from isolated calf adrenal glomerulosa cells. These drugs were more effective inhibitors of K+-induced secretion than ANG II-induced secretion. However, when the ANG II-induced release of intracellular calcium was blocked by prior treatment of cells with dantrolene, then nitrendipine was equally as effective in blocking ANG II- as K+-induced secretion. On the other hand, the dihydropyridine agonist, BAY K8644, was found to enhance K+-induced secretion to a greater extent than ANG II-induced secretion when the latter was studied in either the absence or presence of dantrolene. It is concluded that K+ and ANG II mobilize calcium from different sources for stimulus-response coupling in these cells and that there is no difference in the sensitivity to nitrendipine of the plasma membrane calcium channels operated by these two different agonists.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1984

Oxygenation of 18-hydroxycorticosterone as the final reaction for aldosterone biosynthesis.

Incubation of 18-hydroxycorticosterone with the sonicated mitochondrial preparation of bovine adrenal glomerulosa tissue leads to the production of aldosterone, as measured by radioimmunoassay. The in vitro production of aldosterone from 18-hydroxycorticosterone requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide. Cytochrome P-450 inhibitors such as metyrapone, SU 8000, SU 10603, SKF 525A, amphenone B and spironolactone decrease the biosynthesis of aldosterone from 18-hydroxycorticosterone. These results support the conclusion that the final reaction in aldosterone synthesis from 18-hydroxycorticosterone is catalyzed by an oxygenase, but not by 18-hydroxysteroid dehydrogenase. By the same preparation, the production of [3H]aldosterone but not [3H]18-hydroxycorticosterone from [1,2-3H]corticosterone is decreased in a dose-dependent manner by addition of non-radioactive 18-hydroxycorticosterone.

18-Hydroxycorticosterone↗
PubMed1984

Studies on the biosynthesis of carbapenem antibiotics. I. Biosynthetic significance of the OA-6129 group of carbapenem compounds as the direct precursors for PS-5, epithienamycins A and C and MM 17880.

Based on the working hypothesis that the OA-6129 group of carbapenem compounds might be the direct precursors for PS-5, epithienamycins A and C and MM 17880, Streptomyces fulvoviridis A933 17M9, a producer of PS-5, PS-6, PS-7, PS-8, epithienamycins A, B, C and D, MM 17880, MM 13902 and MM 4550, was subjected to NTG-mutation to provide a blocked mutant numbered 1501 which was found to produce OA-6129 A, OA-6129B1, OA-6129B2 and OA-6129C instead of PS-5, epithienamycins A and C and MM 17880, respectively. In a cell-free system, the parent strain demonstrated an ability to convert OA-6129A to NS-5, whereas the mutant did not. The L- and D-amino acid acylases were also shown to depantothenylate the OA-6129 group of carbapenems.

Amidohydrolases↗
PubMed1984

Calcium as intracellular messenger: sensitivity modulation, C-kinase pathway, and sustained cellular response.

A model of information flow in the calcium messenger system is presented. When Ca2+ serves as an intracellular messenger in cells exhibiting a sustained response to an extracellular messenger, there are two branches by which information flows from cell surface to cell interior: One operates via amplitude modulation of calmodulin-regulated reactions and the other via sensitivity modulation of the calcium-sensitive, phospholipid-dependent protein kinase, C-kinase. It is postulated that the calmodulin branch is largely responsible for initiating, and the C-kinase branch for sustaining, cellular response in cells displaying sustained responses. The role of the C-kinase branch in the calcium messenger system provides a type of gain control in the process of cell activation. It is but one element of several which provides a considerable degree of plasticity in the operation of this cellular control system. Both cAMP and the biologically active intermediates of arachidonic acid metabolism--prostaglandins, thromboxanes, prostacyclin, and leukotrienes--provide additional inputs into this messenger system and a means of extending its adaptability to specific control needs. In particular, in some cell types it is possible that the cAMP messenger system provides the means of achieving gain control in the calcium messenger system either as an alternative to the C-kinase branch of the calcium messenger system or as a supplemental pathway to it.

Animals↗
PubMed1983

Aldosterone secretion: effect of phorbol ester and A23187.

The effects of the divalent ionophore, A23187, the phorbol ester, and/or 12-0-tetradecanoyl-phorbol-13-acetate on aldosterone secretion from adrenal glomerulosa cells were compared to those of angiotensin II (AII). AII causes a prompt and sustained increase in secretion. A23187 causes an initial increase followed by a gradual decline to values less than 25 percent of those seen with AII. TPA causes no initial increase but a slowly progressive rise in secretion rate to a less than maximal value. When TPA and A23187 act together, there is a prompt and sustained increase in aldosterone production rate similar to that seen after AII addition. The effect of TPA is dependent on the free Ca2+ concentration of the cell cytosol. These results are interpreted in terms of a model of cell activation in which two branches of the calcium messenger system operate to control respectively the initial and sustained phases of the secretory response. The first phase occurs as a consequence of amplitude modulation of the calmodulin branch of the system by a rise in [Ca2+]c, and the second phase as a consequence of the sensitivity modulation of the C-kinase branch by diacylglycerol.

Adrenal Medulla↗
PubMed1983

Thermodynamics of distribution of p-substituted phenols between aqueous solution and organic solvents and phospholipid vesicles.

The distribution of p-substituted phenols between 0.15 M NaCl and a range of organic solvents (including 1-octanol) was examined over a range of temperatures. The thermodynamic parameters of transfer, delta G, delta H, and delta S, were determined and the values examined in the light of Hildebrand and Scott's solubility parameter theory, and the collision complexes between solute and organic solvent. Delta H of transfer was positive for nonpolar solvents and negative for 1-octanol; the transfer processes were entropy and enthalpy dominated, respectively. The distribution of the phenols into phospholipid vesicles was examined below the phase-transition temperature. Although delta G of transfer for vesicle-water systems was similar to that for octanol-water systems, the full thermodynamic analysis indicated that the two systems were dissimilar. The use of vesicle distribution data in structure-activity studies is discussed.

Phenols↗