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K Törnquist

Publications and source records attributed to K Törnquist.

68 records · Page 4Linked to original sources

1,25-Dihydroxycholecalciferol enhances both the bombesin-induced transient in intracellular free Ca2+ and the bombesin-induced secretion of prolactin in GH4C1 pituitary cells.

In GH4C1 rat pituitary cells, 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] enhances both the synthesis of PRL and the TRH-induced transient increase in cytosolic free calcium ( [Ca2+]i). In the present report we investigated whether 1,25-(OH)2D3 could enhance the effect of the tetradecapeptide bombesin (BBS) in GH4C1 cells. Pretreatment of the cells with 1 nM 1,25-(OH)2D3 for 24 h enhanced the BBS-induced transient increase in [Ca2+]i compared to that in control cells, while having no significant effect on the plateau phase of [Ca2+]i. Addition of the Ca2+ channel blocker nimodipine or chelating extracellular Ca2+ with EGTA did not abolish the enhancement of the BBS response in 1,25-(OH)2D3-pretreated cells. Furthermore, the BBS-induced efflux of 45Ca2+ from cells preequilibrated with 45Ca2+ was larger in cells treated with 1,25-(OH)2D3. Incubating GH4C1 cells with 1,25-(OH)2D3 alone or in combination with BBS for up to 72 h did not stimulate synthesis of PRL. However, the BBS-induced secretion of PRL was enhanced in cells pretreated with 1,25-(OH)2D3 for 24 h compared with that in vehicle-treated control cells. The effect of 1,25-(OH)2D3 on BBS-induced secretion was dose dependent, with 10(-11) M 1,25-(OH)2D3 enhancing the stimulated secretion of PRL. We conclude that in GH4C1 cells, pretreatment with 1,25-(OH)2D3 enhances the BBS-induced transient increase in [Ca2+]i. This effect may be due to a modulation of the availability of sequestered intracellular Ca2+ and/or membrane Ca2+ conductance. Furthermore, pretreatment with 1,25-(OH)2D3 enhanced secretion of PRL stimulated by BBS. The enhanced transient increase in [Ca2+]i may be the factor inducing the enhanced BBS-induced secretion of PRL.

Animals↗

Priming effect of hyperosmotic stress on TRH-induced activation of Na+/H+ exchange in GH4C1 rat pituitary cells.

The effect of mild hyperosmotic stress on cytosolic pH (pHi) alone, and in combination with thyrotropin-releasing hormone (TRH) or the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was investigated in GH4C1 cells at resting pHi. Hyperosmotic stress induced by addition of 50 mM choline was without an effect on pHi. In cells stimulated with either TRH or TPA after choline, pHi increased 0.15 +/- 0.05 and 0.14 +/- 0.03 pH units, respectively (mean +/- SD). A similar response was obtained if TRH or TPA was added prior to choline. The effect was abolished by replacing extracellular Na+ with choline+, and by pretreatment of the cells with amiloride, indicating that the change in pHi probably was dependent on activation of Na+/H+ exchange. The results thus indicate that, in GH4C1 cells, hyperosmotic stress in combination with TRH or TPA can activate Na+/H+ exchange at resting pHi levels.

Animals↗

Effects of vitamin D3 metabolites on thyrotropin secretion from rat pituitary cells in culture.

The effects of several vitamin D3 metabolites on TSH secretion were investigated using rat pituitary cells in culture. After a 24-h incubation in Dulbecco's medium, only 25,26-dihydroxyvitamin D3 [25,26(OH)2D3] at 10(-6) M increased the basal TSH secretion (36% above control). The TRH-induced TSH secretion increased dose-dependently with increasing concentrations of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] showing a significant increase at 10(-8) M (41% above control). At 10(-5) M 25,26(OH)2D3 the TRH-stimulated TSH secretion was also increased (63% above control). In medium containing charcoal-treated serum, 1, 24,25-trihydroxyvitamin D3 [1,24,25(OH)3D3] decreased the TRH-induced TSH secretion dose dependently (34% below control at 10(-8) M), while the effects of both 1,25(OH)2D3 and 25,26(OH)2D3 were blunted. Our results indicate that several vitamin D3 metabolites may affect pituitary TSH secretion.

24,25-Dihydroxyvitamin D 3↗

Sensitivity, specificity, and predictive value in Katz's and Barthel's ADL indices applied on patients in long term nursing care.

There are propositions that two indices of ADL ability, Katz's and Barthel's indices, are exchangeable for each other. Here this is investigated with regard to clinical applicability. The indices are applied on a material of 23 long term care patients. Sensitivity, specificity, predictive value and interassociations are calculated between the indices, and between indices, nurses' judgements of appropriate care level, an index of cognitive ability (PTS), and a physical examination. Results show clear differences between the indices as to specificity and predictive value, plus differences in sensitivity on dichotomised measurement level. Associations between measures are very high, between measures and nurses' judgements and PTS medium high, and low between indices and physical status. It is concluded that the Katz's ADL index should be preferred in a clinical decision-making for appropriate care level.

Activities of Daily Living↗

Testing daily functions post-stroke with standardized practical equipment.

Two hundred and seven stroke patients were tested with Standardized Practical Equipment (SPE) three months after a stroke. One year after the stroke 183 survivors from this stroke population were tested with the equipment. The SPE test consists of 12 common daily activities, which the patient was asked to perform. The construct validity of SPE was estimated by factor analysis from the results of one-year follow-up. Three factors explained 82% of the variance of the 12 variables of SPE. Factor 1 mainly concerned cognitive factors and co-ordination, Factor 2 construction and hand function and Factor 3 variables that were dependent on mobility and balance. No significant difference was noted between the performance with SPE three months and one year after the stroke among the one-year survivors. There were some differences between men and women; for example the men were more successful in tasks with technical components. The women had more difficulty with some of the tasks involving mobility, such as climbing stairs without support. The Standardized Practical Equipment gave good additive information about the ability of a stroke patient to manage at home and could be used in any set-up.

Activities of Daily Living↗

Cardiovascular effects of the novel cardiotonic agent DPI 201-106 in the anaesthetized rat.

DPI 201-106 (4-[3-(4-diphenylmethyl-1-piperazinyl)-2-hydroxypropoxy]-1H-indole -2- carbonitrile) was given intravenously to anaesthetized male rats. DPI caused an increase in left ventricular dP/dt (LV dP/dt), giving a significant increase at 0.03 mumol/kg. At this dose DPI had no effect on either mean arterial pressure (MAP) or heart rate (HR). At higher doses, MAP decreased transiently. At 0.3 and 1 mumol/kg, HR was decreased. The results indicate that DPI produces positive inotropic and negative chronotropic effects in the anaesthetized rat.

Animals↗

Inhibition of cardiac phosphodiesterase III by the novel cardiotonic agent 6-[4-(4'-pyridyl)aminophenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride.

The novel cardiotonic agent 6[4-(4'-pyridyl)aminophenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride (MCI-154) was investigated for its cardiovascular effects and its mechanism of action. In the anaesthetized rat MCI-154 (0.01-0.3 mumol/kg i.v., bolus injection) produced a dose-dependent increase in left ventricular dP/dt, and a decrease in mean arterial pressure. A relatively small increase in heart rate was observed. The drug inhibited selectively canine cardiac phosphodiesterase III (IC50 2.5 +/- 0.6 mumol/l). In skinned porcine trabeculae, MCI-154 produced only a small increase in the Ca2+-sensitivity of the contractile proteins. The results suggest that MCI-154 is a potent cardiotonic agent, and that inhibition of phosphodiesterase III may be a important component of this effect.

3',5'-Cyclic-AMP Phosphodiesterases↗

The effect of 1,25-dihydroxy-cholecalciferol on the TRH induced TSH release in rats.

The effect of 1,25-dihydroxy-vitamin D3 (1,25-(OH)2-D3) on the TRH induced TSH release was investigated. Wistar rats were injected with 1,25-(OH)2-D3 (0.05 microgram/kg/day) for three days, and TRH was injected iv on the third day. Blood was drawn every 10 min during the following 40 min, and TSH was determined. The TSH release was significantly higher in rats treated with 1,25-(OH)2-D3 than in controls. The rats treated with 1,25-(OH)2-D3 were hypercalcaemic and thus, in order to find out if the effect was mediated through hypercalcaemia rats treated as above, were infused with EDTA (30 mg/kg/100 min) starting 60 min before the TRH test. This treatment made the rats normocalcaemic, and the significant increase in the TSH release was still seen in the 1,25-(OH)2-D3 treated rats as compared to controls. The results thus indicate that 1,25-(OH)2-D3 enhances the TRH induced TSH release and that the effect is not mediated through an increase in the serum calcium concentration at the time of the TRH test. In order to find out if the effect could be mediated by changes in intracellular calcium the rats were treated with the calcium antagonist verapamil (25 mg/kg/day) and the adrenergic blocker propranolol (5 mg/kg/day) alone or together with 1,25-(OH)2-D3. In rats treated with verapamil or propranolol alone or 1,25-(OH)2-D3 + propranolol, no effect was observed on the TRH induced TSH release. Verapamil + 1,25-(OH)2-D3 significantly increased the TSH release as compared to both controls and rats treated with 1,25-(OH)2-D3 alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of 1,25-dihydroxyvitamin D3 on TSH secretion from rat pituitary cells in culture.

The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on TSH secretion from rat pituitary cells was studied. When incubating cells with 1,25(OH)2D3 even at 100 X the physiological concentrations (10(-8)), no effect on basal TSH secretion was observed. The TRH-induced TSH secretion increased after a 24-h incubation with 10(-8) mol/l 1,25(OH)2D3 (2.9 +/- 0.2 ng/well vs 4.3 +/- 0.5 ng/well, mean +/- SD; P less than 0.05). When serum was omitted from the incubation medium, the potentiating effect of 1,25(OH)2D3 on the TRH-induced TSH release was blunted. No effect on cellular protein content was observed after incubating the cells with 10(-8) mol/l 1,25(OH)2D3. The results indicate that at unphysiological concentrations, 1,25(OH)2D3 affects the TRH-induced TSH secretion from pituitary cells. The physiological significance remains unclear.

Animals↗

Systemic effects of 1,25-dihydroxyvitamin D3 on the pituitary-hypothalamic axis in rats.

Treatment of rats with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) 0.05 microgram/kg per day for three days was without any effect on serum T3, T4 or TSH concentrations, whereas serum PRL increased (20.6 +/- 3.8 to 76.2 +/- 19.1 micrograms/l, mean +/- SEM, N = 7-8; P less than 0.01). Increased hypothalamic TRH levels (24.3 +/- 3.9 to 45.7 +/- 7.8 pmol/g wet weight; P less than 0.01) may indicate an effect of 1,25(OH)2D3 on hypothalamic TRH homeostasis. This effect could probably be due to an indirect action of 1,25(OH)2D3, mediated by the increased serum calcium (2.77 +/- 0.02 to 3.16 +/- 0.08 mmol/l, mean +/- SEM, N = 7-8; P less than 0.001). This assumption was, however, not tested. Neither the pituitary TSH nor PRL was affected. The treatment decreased the serum concentration of 25-hydroxyvitamin D3 (23.0 +/- 1.3 to 16.8 +/- 2.0 nmol/l, mean +/- SEM, N = 5-7; P less than 0.01) and of 24,25-dihydroxyvitamin D3 (3.2 +/- 0.3 to 2.1 +/- 0.1 nmol/l, mean +/- SEM, N = 3-5; P less than 0.05). The results show that in this experimental design, 1,25(OH)2D3 has no effect on basal hormone secretion from the pituitary-thyroid axis, and that 1,25(OH)2D3 decreases the synthesis of the vitamin D3 metabolites studied.

Animals↗

Effect of 1,25-dihydroxyvitamin D3 on rat pituitary prolactin release.

The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on PRL secretion from rat pituitary in vivo and in vitro was investigated. Treating the rats for three days with 0.05 microgram/kg per day had no effect on basal PRL secretion, whereas the TRH-induced PRL secretion was increased (P less than 0.001). The enhancing effect of 1,25(OH)2D3 was blunted by verapamil. Incubating dispersed anterior pituitary cells with 10(-8) mol/l 1,25(OH)2D3 induced a significant increase in PRL secretion after 96 h (364 +/- 30 ng/well vs 481 +/- 33 ng/well, P less than 0.001; mean +/- SEM) compared with control cells. The TRH-induced PRL secretion was increased in cells incubated with 1,25(OH)2D3 for 144 h (0.766 +/- 0.061 vs 1.024 +/- 0.076 microgram/well, P less than 0.05; mean +/- SEM) compared with control cells. Neither 25-hydroxyvitamin D3 (25OH-D3) nor 24,25-dihydroxyvitamin D3 had any effects on the PRL secretion. However, when the cells were incubated with both 10(-8) mol/l 1,25(OH)2D3 and 10(-6) mol/l 25OHD3, the enhancing effect of 1,25(OH)2D3 on the basal PRL secretion was blunted. The results suggest that 1,25(OH)2D3 possibly affects the regulation of PRL release from the rat pituitary and that this effect is specific for 1,25(OH)2D3.

Animals↗

Effect of 1,25(OH)2D3 on the TSH secretion from rat pituitary cells.

1,25(OH)2D3 slightly increases basal TSH in the incubation media after a 24 h incubation with increasing amounts of the hormone. The TRH induced TSH response increased significantly in the presence of 10(-8)M 1,25(OH)2D3 (P less than 0.05). The intracellular concentration of TSH after the TRH test showed a slight decreasing tendency after a 24 h incubation with increasing amounts of 1,25(OH)2D3. The presence of verapamil (10(-8) M) and propranolol (10(-8) M) blunted the enhancing effect of 1,25(OH)2D3. The results indicate an effect of 1,25(OH)2D3 on the secretion of TSH.

Animals↗