The effect of plasma potassium in determining normal rates of excretion of potassium in dogs.
(9/1163)
Doses of 5-15 mmol KCl or KHCO3 (less than the daily intake in food) given by stomach tube or intravenous infusion, produced increases in plasma K and in K excretion, the time delay between change in plasma K and rate of excretion being minimal. Without doses of K salts in control experiments, plasma K concentration was about 4 mmol/1 and K excretion about 5 mumol/min. After doses of KCl or KHCO3, plasma K and rate of excretion of K both increased, increase of 0-5 mmol/1 in plasma K being associated with an increase of about 35 mumo1/min in K excretion. Increased excretion of K was accompanied by a small increase in Na excretion. Excretion of both C1 and HCO3 increased, C1 more after HCO3 more after KHCO3. The results indicate that within normal ranges, plasma K is an important factor determining the rate of excretion of K. (+info)
A defect late in stimulus-secretion coupling impairs insulin secretion in Goto-Kakizaki diabetic rats.
(10/1163)
A widely accepted genetically determined rodent model for human type 2 diabetes is the Goto-Kakizaki (GK) rat; however, the lesion(s) in the pancreatic islets of these rats has not been identified. Herein, intact islets from GK rats (aged 8-14 weeks) were studied, both immediately after isolation and after 18 h in tissue culture. Despite intact contents of insulin and protein, GK islets had markedly deficient insulin release in response to glucose, as well as to pure mitochondrial fuels or a non-nutrient membrane-depolarizing stimulus (40 mmol/l K+). In contrast, mastoparan (which activates GTP-binding proteins [GBPs]) completely circumvented any secretory defect. Basal and stimulated levels of adenine and guanine nucleotides, the activation of phospholipase C by Ca2+ or glucose, the secretory response to pertussis toxin, and the activation of selected low-molecular weight GBPs were not impaired. Defects were found, however, in the autophosphorylation and catalytic activity of cytosolic nucleoside diphosphokinase (NDPK), which may provide compartmentalized GTP pools to activate G-proteins; a deficient content of phosphoinositides was also detected. These studies identify novel, heretofore unappreciated, defects late in signal transduction in the islets of our colony of GK rats, possibly occurring at the site of activation by NDPK of a mastoparan-sensitive G-protein-dependent step in exocytosis. (+info)
Effect of transport on pulsatile and surge secretion of LH in ewes in the breeding season.
(11/1163)
The aim of this study was to elucidate the mechanism(s) involved in stress-induced subfertility by examining the effect of 4 h transport on surge and pulsatile LH secretion in intact ewes and ovariectomized ewes treated with steroids to induce an artificial follicular phase (model ewes). Transport caused a greater delay in the onset of the LH surge in nine intact ewes than it did in ten ovariectomized ewes (intact: 41.0 +/- 0.9 h versus 48.3 +/- 0.8 h, P < 0.02; ovariectomized model: 40.8 +/- 0.6 h versus 42.6 +/- 0.5 h, P < 0.02). Disruption of the hypothalamus-pituitary endocrine balance in intact ewes may have reduced gonadotrophin stimulation of follicular oestradiol production which had an additional effect on the LH surge mechanism. In the ovariectomized model ewes, this effect was masked by the exogenous supply of oestradiol. However, in these model ewes, there was a greater suppression of maximum LH surge concentrations (intact controls: 29 +/- 4 ng ml-1 versus intact transported 22 +/- 5 ng ml-1, P < 0.02; ovariectomized model controls: 35 +/- 7 ng ml-1 versus model transported 15 +/- 2 ng ml-1, P < 0.02). Subsequent exposure to progesterone for 12 days resulted in the resumption of a normal LH profile in the next follicular phase, indicating that acute stress leads to a temporary endocrine lesion. In four intact ewes transported in the mid-follicular phase, there was a suppression of LH pulse amplitude (0.9 +/- 0.3 versus 0.3 +/- 0.02 ng ml-1, P < 0.05) but a statistically significant effect on pulse frequency was not observed (2.0 +/- 0.4 versus 1.7 +/- 0.6 pulses per 2 h). In conclusion, activation of the hypothalamus-pituitary-adrenal axis by transport in the follicular phase of intact ewes interrupts surge secretion of LH, possibly by interference with LH pulsatility and, hence, follicular oestradiol production. This disruption of gonadotrophin secretion will have a major impact on fertility. (+info)
Effect of transport on pituitary responsiveness to exogenous pulsatile GnRH and oestradiol-induced LH release in intact ewes.
(12/1163)
This study examined the effect of transport on GnRH self-priming in vivo as well as the consequential effects on the oestradiol-induced LH surge. The follicular phases of ewes (eight per group) were synchronized with progestin sponges, and 50 micrograms oestradiol benzoate was injected 24 h (time zero) after sponge removal to improve precision in the timing of the LH surge. Beginning 8 h after oestradiol, saline or GnRH (500 ng, i.v.) was given at 2 h intervals with or without 8 h transport beginning 0.5 h before the first GnRH injection (late transport) and effects were compared with those observed during early transport, that is, starting 2.5 h before the first GnRH injection. In all ewes, GnRH alone induced a maximum LH response of 1.9 +/- 0.4 ng ml-1 after the first challenge. The response was enhanced (P < 0.01) after the second and third GnRH injections (7.4 +/- 1.4 ng ml-1 and 7.6 +/- 1.7 ng ml-1, respectively). This self-priming effect after the second GnRH was reduced by late transport (7.4 +/- 1.4 versus 4.2 +/- 0.8 ng ml-1; P < 0.05) but not early transport, that is, transport initiated closer to the time of GnRH administration had greater suppressive effects on LH secretion. Throughout transport, spontaneous LH pulse frequency was lower in treated than it was in control ewes (2.38 +/- 0.53 versus 4.50 +/- 0.53 pulses per 8 h; P < 0.01), with marked effects in the first 4 h of transport (1.0 +/- 0.19 versus 2.63 +/- 0.38 pulses per 4 h; P < 0.02). Spontaneous pulse amplitude also tended to decrease during transport (0.13 +/- 0.02 versus 0.20 +/- 0.03 ng ml-1; P = 0.07). When LH turnover was stimulated by exogenous GnRH, the onset of the LH surge was delayed (controls: 20.5 +/- 2.0 h versus GnRH alone: 25.3 +/- 1.5 h; P < 0.05) and the duration was reduced (8.5 +/- 0.9 versus 6.5 +/- 0.4 h; P < 0.05). Transport tended to delay the LH surge in saline-treated ewes (20.5 +/- 2.0 versus 22.9 +/- 1.9 h; P = 0.08), with a further delay imposed by late transport plus GnRH (27.5 +/- 1.6 h; P < 0.05) but not by early transport plus GnRH (27.8 +/- 2.5 versus 26.4 +/- 2.4 h; P > 0.05), that is, effects mediated by increasing LH turnover were only manifest if transport occurred near the LH surge, when there was insufficient time to replenish stores of releasable LH. In all transported ewes, plasma cortisol increased from 4.5 +/- 1.0 ng ml-1 to 29.2 +/- 5.5 ng ml-1 (P < 0.001) within 15 min of the start of transport and was significantly lower (P < 0.01) by 6.5 h. Plasma progesterone also increased from 0.30 +/- 0.04 to 0.38 +/- 0.04 ng ml-1 (P < 0.05). In conclusion, transport affected the oestradiol-induced LH surge by causing a 50% reduction in the self-priming effect of exogenous GnRH, but hypothalamic effects were also revealed by a two-fold decrease in spontaneous LH pulse frequency in saline-treated ewes. (+info)
Changes in metabolism of TRH in euthyroid sick syndrome.
(13/1163)
OBJECTIVE: The aim of this study was to examine the metabolism of a simple dose, intravenously administered TRH bolus of 200 microg, in patients with euthyroid sick syndrome (ESS). PATIENTS AND METHODS: A TRH test was performed on ten ESS patients and ten controls upon admission (d1) and after recovery (d2). Blood samples were collected at 0, 10, 20 and 30min after TRH injection. We analyzed the volume of distribution (V(d)), the plasma clearance rate (PCR), the fractional clearance rate (FCR), the half-life (t(1/2)) and the TSH response to the injection of TRH. RESULTS: All patients had lower tri-iodothyronine (T(3)) levels compared with controls (0.9 +/- 0. 1nmol/l vs 1.9 +/- 0.1 nmol/l; P < 0.0001; mean +/- S.D.; paired t-test). In addition, the V(d) (16.7 +/- 5.9/l vs 30.6 +/- 0.6/l; P < 0.0005) and PCR (2.0 +/- 0.80 l/min vs 3.3 +/- 0.25 l/min; P <0. 0005) were found statistically lowered in patients than in controls, whereas FCR (0.119 +/- 0.01 permin vs 0.110 +/- 0.01 per min; P < 0. 025) was found increased in patients as opposed to controls. The t(1/2) of exogenously administered TRH was increased in ESS compared with controls (7.2 +/- 0.7 min vs 6.3 +/- 0.6 min; P <0.005). TSH response to TRH was found significantly repressed at 10, 20 and 30 min after TRH injection. On d2, these findings had reverted to normal and no changes regarding the kinetics of TRH and the response of TSH could be detected between patients and controls. CONCLUSIONS: The results demonstrate an impairment of TRH metabolism in ESS. The findings may suggest altered enzymatic activity, responsible for TRH degradation in states of acute ESS. These changes might be involved in the pathogenesis of ESS and represent part of an adaptive mechanism to this syndrome. (+info)
Dopamine agonists both stimulate and inhibit prolactin release in GH4ZR7 cells.
(14/1163)
Prolactin secretion from the anterior pituitary gland is regulated by multiple factors including prolactin-release inhibiting factors (PIFs) and prolactin releasing factors. PIFs, however, usually dominate to exert a tonic inhibition in the biological system, and the physiological PIF is believed to be dopamine. However, there is accumulating evidence that dopamine can not only inhibit but also stimulate prolactin release. Many investigators believe that this is achieved by activating inhibitory and stimulatory subtypes of dopamine receptors. We tried to demonstrate that one subtype of dopamine receptors is capable of both inhibiting or stimulating prolactin release using GH(4)ZR(7) cells. GH(4)ZR(7) cells express only a short form of dopamine D(2) receptors (D(2s)). Low concentrations of three well-established D(2) receptor agonists (dopamine, apomorphine and bromocriptine) stimulated prolactin release from GH(4)ZR(7) cells while high concentrations inhibited the release. Haloperidol, a D(2) receptor antagonist, blocked the inhibitory action, but was unable to block the dopamine-induced stimulatory action. Pretreatment of cells with phenoxybenzamine, a receptor alkylating agent, abolished both the dopamine-induced stimulatory and inhibitory actions. Our results support the thesis that the stimulation of prolactin release induced by dopamine is mediated through dopamine D(2s) receptors since the GH(4)ZR(7) cells have only D(2s) receptors among dopamine receptors. We have concluded that the D(2s) receptor is capable of both stimulating and inhibiting prolactin release, probably via the activation of a G(s) protein by low concentrations and a G(i) protein by high concentrations of dopaminergic agents. (+info)
Adaptation of pancreatic islet B-cells during the last third of pregnancy: regulation of B-cell function and proliferation by lactogenic hormones in rats.
(15/1163)
In rodents, placental lactogen (PL)-I is considered to be the first trigger to enhance pancreatic islet B-cell function, and after its secretion is diminished at mid-pregnancy, PL-II takes over this role. However, little information is available on the regulation of islet B-cell function and proliferation by lactogenic hormones during the last third of pregnancy. This was the focus of the present study using rats in which pregnancy was forcibly prolonged. This rat possesses unique characteristics in that PL-I is re-secreted during the prolonged period of pregnancy and the peak concentrations in maternal circulation are comparable with those observed during mid-pregnancy in normal-pregnancy rats. Pregnancy was prolonged by successive administration of pregnant mare's serum gonadotropin (30IU/rat, s.c. on day 12) and human chorionic gonadotropin (10IU/rat, i.v. on day 14). When the insulin secretory responses to 10mmol/l glucose in islets obtained from normal-pregnancy and prolonged-pregnancy rats were tested, each insulin secretory response correlated well with the values of plasma lactogenic activity throughout the period of pregnancy and lactation. Examination of B-cell proliferation in normal-pregnancy rats showed that 5-bromo-2'-deoxyuridine (BrdU) incorporation into dividing B-cells reached a maximum on day 15 and then decreased markedly towards term. No increase in B-cell proliferation was observed on day 19 when plasma lactogenic activity reached the maximum. In prolonged-pregnancy rats, BrdU incorporation also continued to decrease as observed in normal-pregnancy rats after day 15, and then no enhancement in B-cell proliferation was observed even when the plasma lactogenic activity, including re-secreted PL-I, reached maximum. These results suggest that, in the last third of pregnancy, B-cell proliferation is no longer stimulated by lactogenic hormones in contrast to the insulin secretory response which is sustained. (+info)
A structural comparison of lipopolysaccharides from two strains of Helicobacter pylori, of which one strain (442) does and the other strain (471) does not stimulate pepsinogen secretion.
(16/1163)
Lipopolysaccharides (LPSs) from strains of Helicobacter pylori (442 and 471), which differed in stimulation of pepsinogen secretion, were isolated as water-soluble material of high-M(r), and as water-insoluble gels of low-M(r). Chemical and spectroscopic analyses of soluble LPS and oligosaccharides liberated from the gels led to proposed structures with Lewis (Le) antigen termini connected to N -acetyllacto-saminoglycans of alternating 3-linked beta-D-Gal and 4-linked beta-D-GlcNAc residues with various laterally attached glycosyl substituents. The LPS of H.pylori 442 was similar to previously examined strains (NCTC 11637 and P466) in having partially glycosylated chains with alpha-L-Fuc units attached to O-3 of the majority of GlcNAc residues in Le(x)units, and in chain termination with Le(x)or Le(y)determinants. In contrast, terminal Le(y)units occurred in LPS of H.pylori 471 and glycosaminoglycan chains carried a smaller proportion of alpha-L-Fuc units, but at O-6 of a majority of nonfucosylated GlcNAc residues, there was a novel type of branching with alpha-D-Gal substituents. Evidence for the branched regions was obtained from(1)H-NMR spectra and from characterization of oligosaccharides formed by the action of endo-beta-galactosidase. Examination of oligosaccharides liberated from water-insoluble LPS gels of H.pylori 442 and 471 provided evidence for similar core OS structures to those from other H.pylori strains but interesting differences were observed. (+info)