Biomedical subjects

H Plass

Publications and source records attributed to H Plass.

10 recordsLinked to original sources

PubMed1994

Different homologous subunits of the amiloride-sensitive Na+ channel are differently regulated by aldosterone.

Long term regulation of the amiloride-sensitive Na+ channel activity by steroid hormones occurs via de novo protein synthesis. The messenger level of RCNaCh1, previously shown by expression cloning to be a component of this channel, was measured in colons from rats fed with a low sodium diet. After 1 week of this diet, the channel activity was increased in an all-or-none fashion, whereas the level of RCNaCh1 messenger remained constant. A cDNA coding for another subunit of the Na+ channel was obtained by polymerase chain reaction. The 650-amino acid protein, entitled RCNaCh2, is 58% homologous to RCNaCh1 and displays a similar structure. It had no intrinsic activity when expressed alone in Xenopus oocytes, but its co-expression with RCNaCh1 increased the channel activity 18 +/- 5-fold. The increase in messenger level for RCNaCh2 during the time course of the diet is likely to explain the positive regulation of the rat colon Na+ channel by steroids. Immunocytochemical localization of the RCNaCh1 subunit revealed an apical labeling in colon from sodium-depleted rats. No labeling was observed in colon from control animals. These results suggest that oligomerization is needed for the proper expression of RCNaCh1 at the cell surface.

Aldosterone↗

PubMed1994

Neurogenic chloride secretion induced by scorpion venom and veratrine in rabbit colon.

In earlier reconstitution experiments the venom of the scorpion Leiurus quinquestriatus, LQV, was shown to block Ca(2+)-activated high-conductance K+ channels from the basolateral cell membrane of rabbit colonocytes (Turnheim K, Costantin J, Chan S, Schultz SG (1989) J Membrane Biol 112:247-254). These LQV-sensitive K+ channels do not seem to be involved in active Na+ transport across rabbit colon, as absorptive Na+ fluxes were not significantly affected by serosal addition of LQV to isolated epithelia of rabbit descending colon. While Na+ absorption was not changed, LQV and veratrine caused electrogenic Cl- secretion in this tissue by a neural (tetrodotoxin sensitive) mechanism. The secretory effect of LQV was partly inhibited by atropine, suggesting the involvement of m-cholinoceptors, and by a VIP-antagonist. In contrast to the neurogenic secretion in the small intestine of guinea pig, rat and cat, 5-hydroxytryptamine (5-HT) does not seem to be involved in neurogenic secretion in rabbit colon, as 1) several 5-HT receptor antagonists did not inhibit the LQV effect with the exception of high concentrations of tropisetron, 2) exogenous 5-HT had no secretory effect, and 3) there was no significant release of 5-HT from the tissue during neurogenic secretion. The inhibitory effect of tropisetron on intestinal Cl- secretion seems to be unrelated to its property as a 5-HT3 receptor antagonist.

Animals↗

PubMed1992

Vanadium-induced Cl(-)-secretion in rabbit descending colon is mediated by prostaglandins.

Vanadium in the 4+ (vanadyl-ion) and 5+ (vanadate-ion) oxidation state stimulates furosemide-sensitive electrogenic Cl- secretion in isolated epithelia of rabbit descending colon. This effect is associated with an increased release of prostaglandin E2 from the tissue. Inhibitors of phospholipase A2 or cyclooxygenase abolish both vanadium-induced release of prostaglandin E2 and Cl- secretion. Neuronal mechanisms are not likely to be involved, as tetrodotoxin does not affect the vanadate induced Cl- secretion. Although vanadate is known to inhibit Na+,K(+)-ATPase activity, no inhibition of active Na+ transport was observed in intact colonic epithelia suggesting a rapid intracellular reduction of vanadate ions to vanadyl ions which have no inhibitory effect on the Na+,K(+)-ATPase. The present findings therefore indicate that vanadate stimulated colonic Cl- secretion involves intracellular conversion of vanadate to vanadyl and release of prostaglandin E2.

Animals↗

PubMed1992

Endothelin-1 stimulates chloride and potassium secretion in rabbit descending colon.

The vasoactive peptide endothelin-1 (ET-1) which is present in high concentrations in the colon, causes concentration-dependent electrogenic Cl- secretion in rabbit descending colon. This effect is half-maximal at 0.11 mumol/l. Like other secretagogues, ET-1 also stimulates K+ secretion. The secretory effect of ET-1 is associated with increased release of prostaglandin E2 from the serosal surface of the mucosa. ET-1-induced Cl- secretion is completely inhibited by the loop diuretic bumetanide and by indomethacin and quinacrine, inhibitors of prostaglandin synthesis. Neuronal mechanisms do not seem to be involved, as tetrodotoxin did not affect the secretory response to ET-1 significantly. On the other hand, neither the catalytic activity nor the transport function of the Na+/K(+)-ATPase of rabbit colon epithelium is affected by endothelin-1 (ET-1) in concentrations up to 10 mumol/l. It is concluded that ET-1 causes Cl- and K+ secretion by stimulating phospholipase A2 and release of prostaglandins, whereas Na+ transport is not altered.

Animals↗

PubMed1991

Plasma propafenone concentration in the evaluation of anti-arrhythmic efficacy.

The anti-arrhythmic drug efficacy of oral propafenone therapy (300 mg to 900 mg per day) was studied in relation to propafenone and hydroxy-propafenone plasma concentrations in 70 outpatients (46 males, 24 females, mean age 57 +/- 12 years) followed up for 24 +/- 32 months. On average 1.7 plasma concentration measurements were performed per patient. The arrhythmias were effectively controlled in 32 patients, but in another 32 patients propafenone therapy was ineffective; in six patients the evaluation was unclear. The therapy was effective in 66% of patients with ventricular premature beats, in 50% with complex ventricular arrhythmias, in 40% with ventricular tachycardia and in 20% with supraventricular tachycardia. Fifty per cent of patients with coronary heart disease and electrical disease, but only 20% with dilated cardiomyopathy and Wolff-Parkinson-White syndrome were effectively treated. Measurement of peak plasma propafenone levels performed 4.5 +/- 2 h after oral drug administration revealed no statistically significant dose-plasma concentration relation. Optimal propafenone drug efficacy was documented at propafenone plasma concentrations ranging from 0.20 to 0.60 micrograms/ml (63% of patients considered as effectively treated). There was a trend to decrease propafenone efficacy at plasma concentrations below 0.20 micrograms/ml and above 0.60 micrograms/ml. Analysis of hydroxypropafenone identified four patients as poor metabolizers with unusually high propafenone and low hydroxypropafenone plasma concentrations; only one of these four patients showed drug efficacy. Monitoring of propafenone and hydroxypropafenone plasma concentrations was a practical procedure to assess patient's compliance, to identify poor metabolizers and to guide anti-arrhythmic drug therapy.

Adult↗

PubMed1990

[Biological availability of different oral cimetidine preparations in the dog].

Bioavailability of Different Oral Dosage Forms of Cimetidine in Dogs. The bioavailability of cimetidine (200 mg) after oral administration to awake dogs was increased significantly by using tablets containing alginate. In addition the timespan was prolonged during which therapeutic plasma concentrations were maintained. Release and absorption of cimetidine were retarded from tablets containing methacrylic acid-copolymers, but the bioavailability was decreased from this dosage form and therapeutic plasma concentrations were not reached.

Acrylates↗

PubMed1986

Absorption and secretion of potassium by rabbit descending colon.

Measurements of K fluxes under a variety of conditions have provided an internally consistent set of data that demonstrate active absorption and active secretion of K by rabbit descending colon in vitro. The properties of K diffusion across the paracellular pathway are those of a free solution shunt. With Na and Cl present on both sides of short-circuited tissues the two opposing active K transport systems balance each other, so that there is no net K transport. Net K absorption results when the transcellular secretory K flux is inhibited by 1. serosal addition of ouabain, 2. serosal addition of furosemide, or 3. omission of either Na or Cl from the serosal solution. Hence basolateral K uptake appears to be mediated by a furosemide-sensitive Na-Cl-K cotransport system in addition to the Na-K exchange pump. Luminal addition of mersalyl or orthovanadate inhibits active K absorption. The adenosine analogue 5'-N-ethylcarboxamide adenosine and the beta-adrenergic agent isoproterenol, added to the serosal solution, cause net K secretion which is inhibitable by furosemide. The secretory K fluxes, both under stimulated and nonstimulated conditions, are abolished by an opposing electrical gradient, suggesting conductive K exit across the apical cell membrane, whereas K absorption appears to be an electroneutral process.

Absorption↗

PubMed1986

Sodium absorption and potassium secretion in rabbit colon during sodium deficiency.

Reducing the daily Na intake of rabbits from approximately 4.4 to 0.1 meq/kg body wt increases plasma aldosterone levels and the rate of amiloride-sensitive Na transport in the descending colon two- to threefold. The stimulation of Na transport is a result of an increase in the maximum transport capacity of the epithelium, whereas the affinity of Na to its transport system is not altered. Simultaneous with enhanced Na absorption, there is statistically significant K secretion of 0.25 mu eq . cm-2 . h-1 under short-circuit conditions. Transepithelial current-voltage relations in the absence and presence of amiloride were used to determine the Na permeability of the apical membrane and the intracellular Na activity of the Na-transporting cells. The Na content of the amiloride-sensitive cells was estimated from the kinetics of absorptive Na tracer fluxes. The stimulation of active Na transport under conditions of dietary Na restriction is associated with parallel increases in apical membrane Na permeability and the Na content of the amiloride-sensitive cells, but the intracellular Na activity and the activity of the epithelial Na-K-ATPase are not significantly altered. Taken together, these results suggest that endogenous aldosterone increases the number of conducting Na entry sites in the apical membrane of colonic epithelium and that there is activation of additional Na pump units in the basolateral membrane, brought about by cell swelling and possibly by an increase in the fraction of epithelial cells that participate in active Na transport.

Absorption↗

PubMed1985

Determination of the sodium transport pool in epithelia from tracer fluxes: a simplified approach.

The epithelial content of tracer Na can be calculated either from the exponential increase of unidirectional transepithelial Na tracer fluxes observed after addition of labeled Na to the solution bathing the luminal side of isolated epithelia or from the linear portion of the rate of accumulation of label in the serosal solution. The second method is not only simpler, because fewer data points are required and no logarithmic transformations are necessary, but also more accurate, as shown in experiments with stripped epithelia of rabbit descending colon. From the difference in tissue Na tracer content in the absence and presence of amiloride, which blocks luminal Na uptake, a Na concentration in the transport pool of 8-10 mM is obtained, assuming that all cells participate in active transport. From a comparison of the intracellular Na concentration derived from current-voltage relations of the apical Na entry step with the Na concentration in the epithelial Na transport pool, an estimate may be obtained of what fraction of the cell mass is involved in active Na transport.

Amiloride↗

PubMed1984

Phosphorylated adenosine derivatives as low-affinity adenosine-receptor agonists. Methodological implications for the adenylate cyclase assay.

In cellular systems provided with activatory (Ra-site) receptors for adenosine, such as rat cerebral microvessels and rat liver plasma membranes, the adenosine-receptor antagonist 8-phenyltheophylline (10 microM) significantly decreased adenylate cyclase activity if ATP was the substrate and only if GTP was present. With dATP as substrate, adenylate cyclase activities in both preparations remained unaffected by 8-phenyltheophylline. In rat cerebral-cortical membranes, with inhibitory (Ri-site) receptors for adenosine, 8-phenyltheophylline significantly enhanced adenylate cyclase activity only in the presence of GTP and if ATP was the substrate. In rat cardiac ventricular membranes, which are devoid of any adenylate cyclase-coupled adenosine receptor, the methylxanthine had no GTP-dependent effect, irrespective of the substrate used. All assay systems contained sufficiently high amounts of adenosine deaminase (2.5 units/ml), since no endogenous adenosine, formed from ATP, was found chromatographically. In order to demonstrate a direct influence of phosphorylated adenosine derivatives on adenylate cyclase activity, we investigated AMP in a dATP assay system. AMP was verified chromatographically to remain reasonably stable under the adenylate cyclase assay conditions. In the microvessels, AMP increased enzyme activity in the range 0.03-1.0 mM, an effect competitively antagonized by 8-phenyltheophylline. In the cortical membranes, 0.1 mM-AMP inhibited adenylate cyclase, which was partially reversed by the methylxanthine. The presence of GTP was again necessary for all observations. In the ventricular membranes, AMP had no effect. Since the efficacy of adenosine-receptor agonists and, probably, that of other hormones on adenylate cyclase activity can be more efficiently measured with dATP as the enzyme substrate, this nucleotide seems preferable for adenylate cyclase measurements in systems susceptible to modulation by adenosine.

Adenine Nucleotides↗