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K A Munday

Publications and source records attributed to K A Munday.

At least 19 recordsLinked to original sources
PubMed1987

The effect of angiotensin II upon electrogenic ion transport in rat intestinal epithelia.

Epithelial sheets from rat jejunum and descending colon have been shown to respond to angiotensin II (AII) when studied under short-circuit conditions and bathed on both sides with Krebs-Henseleit solution. The octapeptide AII elicited increases in short-circuit current (SCC) in preparations of jejunum and decreases in SCC in the descending colon; both responses occurred when the peptide was applied to the basolateral surface, but not when applied to the apical solution. Responses in both tissues were highly specific, being inhibited by a range of AII antagonists with the following order of potency: [Sar1. Thr8]-AII greater than [Sar1. Leu8]-AII greater than [Sar1. Ile8]-AII greater than [Sar1. Ala8]-AII greater than [Des,Asp1. Ile8]-AII in rat jejunum. AII responses were not affected by alpha- or beta- adrenoceptor antagonists, atropine or tetrodotoxin. AII responses were totally inhibited by the chloride channel blocker, diphenylamine-2-carboxylate (DPC) while cotransport inhibitors e.g. piretanide and frusemide significantly reduced the size of AII responses in colon and jejunum. These patterns of activity suggest that in the jejunum the responses result from electrogenic chloride secretion. Although AII responses in colon were sensitive to DPC the transporting ions have not yet been identified. Both piroxicam and indomethacin inhibited the increase in SCC elicited by AII in the jejunum, and the reduction in SCC caused by AII in the colon. Taken together these results indicate that eicosanoids are involved in AII responses in both tissues. This is the first study to demonstrate a direct, electrogenic effect for AII on transporting epithelia from the gastrointestinal tract. The responses are most probably initiated by All interacting with previously identified specific All receptors within the epithelial membranes.

Angiotensin I↗
PubMed1986

Identification of selective, high affinity [125I]-angiotensin and [125I]-bradykinin binding sites in rat intestinal epithelia.

Specific [125I]-angiotensin II (AII) and [125I]-bradykinin (Bk) binding sites have been identified within epithelial membranes from rat jejunum and descending colon. These high affinity intestinal sites exhibited KD values of 0.64 +/- 0.16 nM for [125I]-AII and 0.69 +/- 0.13 nM for [125I]-Bk, which were similar to those for [125I]-AII (0.85 nM) and [125I]-Bk binding sites (1.03 nM) previously identified in renal cortex epithelia. Specific [125I]-AII binding capacity was only 19.77 +/- 2.74 fmol mg-1 in small intestine and 11.31 +/- 2.66 fmol mg-1 in descending colon epithelia while a larger population, 332.0 +/- 72.9 fmol-mg-1 of specific [125I]-Bk sites were identified in epithelial membranes from small intestine. Significant hydrolysis of both free [125I]-AII and [125I]-Bk was observed while membrane bound peptides remained relatively resistant to degradation. Whilst no corrections have been made to the observed values of KD and Bmax quoted above, one may assume that the calculated reductions in the free hormone concentration will result in a decrease of the KD value for both peptides. Loss of membrane bound peptide, particularly of [125I]-AII, may indicate that the calculated Bmax value is an underestimation. Despite the rapid degradation of unbound [125I]-AII and [125I]-Bk during incubations the kinetics of specific peptide binding were reversible and highly selective. The order of potency for specific [125I]-AII binding was [Sar1, Leu8]-AII greater than or equal to [Sar1, Thr8]-AII greater than or equal to AII greater than [Sar1, Ile8]-AII greater than or equal to [Des, Asp1, Ile8] AII greater than AIII. Specific [125I]-Bk binding was also highly selective, the order of potency being Phe8-Bk greater than or equal to Tyr8-Bk greater than or equal to Lys-Bk much greater than Des, Arg1-Bk. AII exhibited an IC50 of greater than 1mM for specific [125I]-Bk binding and likewise Phe8-Bk for specific [125I]-AII binding.

Angiotensin II↗
PubMed1984

Inactivation of [125I]-angiotensin II binding sites in rat renal cortex epithelial membranes by dithiothreitol.

Preincubation of renal epithelial membranes with DTT produced a dose-dependent inhibition of specific [125I]-angiotensin binding, with an IC50 of 1 mM and total loss of binding at 5-10 mM DTT. Inactivation of specific [125I]-angiotensin II binding by DTT was temperature sensitive; the t1/2 at 22 degrees was 6 min compared with 30 min at 4 degrees. A rapid inactivation rate was dependent on the presence of NaCl. In the presence of 120 mM NaCl the t1/2 for inactivation by DTT was 6 min and 33 min in the absence of NaCl. Protection against DTT inactivation was obtained by preincubating membranes with unlabelled angiotensin II greater than angiotensin I greater than renin substrate while the dipeptide, Ileu-His was only effective in protecting the binding site at high concentrations (10 mM). Preincubations with DTT (1 mM) caused a 43% decrease in Bmax from 217.0 +/- 39.5 to 123.7 +/- 30.9 fmol bound/mg protein while the KD was not significantly affected.

Angiotensin II↗
PubMed1984

The binding of [3H]prazosin and [3H]clonidine to rat jejunal epithelial cell membranes.

The binding of [3H]prazosin and [3H]clonidine to rat jejunal epithelial cell membranes has been studied. The membrane preparation was enriched in baso-lateral components as determined by Na+, K+ ATPase and alkaline phosphatase activities. The membranes possessed two saturable specific binding sites for [3H]prazosin, a high affinity (Kd 0.17 nM) low capacity (Bmax 27.3 fmole bound per mg protein) and a low affinity (Kd 5.0 nM) high capacity (Bmax 276 fmole bound per mg protein) site. The specificity of both sites was similar and was related to alpha 1-adrenoceptors. [3H]Clonidine bound to the membranes in a saturable fashion (Kd 7.3 nM). The specificity of this site was related to alpha 2-adrenoceptors. The [3H]clonidine binding site was present in the membranes in much lower density (Bmax 22.8 fmole bound per mg protein) suggesting that alpha 1-adrenoceptors predominate in this tissue.

Animals↗
PubMed1984

The renal, cardiovascular and hemolytic actions in the rat of a toxic extract from the bile of the grass carp (Ctenopharyngodon idellus).

Grass carp bile, sometimes eaten by Chinese people, has previously been shown to induce acute renal failure in man and to result in the death of experimental mice and rats. A toxic extract from the bile acid fraction of grass carp bile (LD50 109 mg/kg) was injected into pentobarbitone anesthetized rats and an increase in urinary excretion of water and salts was produced. The bile extract also caused a prompt fall in systemic arterial blood pressure and cardiac output. It was also found, in vitro, that the bile salts caused a potent hemolysis. The hypothesis that hemoglobin is released from hemolysed red blood corpuscles and might be responsible for the long term renal functional damage is considered. Another alternative hypothesis is that the hypotension induced by the bile toxin may result in renal underperfusion and thus make the kidney more susceptible to the nephrotoxic action of the grass carp bile.

Animals↗
PubMed1984

Location of [125I]-angiotensin II receptors on rat kidney cortex epithelial cells.

Angiotensin II (AII) stimulates active Na+ extrusion from Na+ loaded renal cortex slices. Specific high affinity [125I]-AII binding sites in partially purified basolateral and brush-border epithelial membranes exhibit a KD of 0.88 nM and Bmax of 321.13 fmol mg-1 protein. Separation and purification of brush-border membranes yielded high affinity [125I]-AII binding sites with KD of 1.02 nM and Bmax of 56.6 fmol mg-1 protein. Angiotensin II receptors of the same affinity are present on renal cortex brush-border and basolateral membranes but a greater proportion are located on the latter. These receptors may be involved in the direct control of Na+ and water transport by AII.

Alkaline Phosphatase↗
PubMed1984

Angiotensin II mediates increased small intestinal fluid absorption with extracellular volume depletion in the rat.

The purpose of this study was to determine if the increase in small intestinal fluid absorption observed after extracellular fluid (ECF) reduction is mediated by angiotensin II (AII). Infusion of AII at doses that increase plasma levels of the hormone within the physiological range stimulates jejunal fluid absorption. In contrast, at pharmacological doses that result in plasma AII levels unlikely to be encountered normally, the hormone inhibits absorption and/or stimulates jejunal secretion. The AII stimulation of jejunal fluid absorption is potentiated by nephrectomy, suggesting that the endogenous levels of AII are related to and have an important role in regulation of the cellular level of its own receptors. Extracellular volume reduction as a result of sodium depletion, nonhypotensive hemorrhage, or water deprivation increases jejunal fluid absorption 30-40% above control values. This increase in jejunal absorption after ECF reduction is not affected by adrenalectomy, but is abolished by nephrectomy, either alone or in combination with adrenalectomy. Captopril, prazosin, and peripheral sympathectomy also abolish the increase in jejunal absorption following ECF depletion. It is suggested that AII is generated after ECF reduction and increases jejunal fluid absorption by facilitating the release of norepinephrine from enteric sympathetic nerves. Thus, AII is a physiologically important mediator of jejunal fluid absorption.

Adrenalectomy↗
PubMed1983

The effect of guanine nucleotides on [125I]-angiotensin binding in rat kidney cortex epithelial membranes.

Specific [125I]-angiotensin binding to crude basolateral/brush border membranes of rat kidney cortex was influenced by guanine nucleotides. The order of potency of nucleotides in their ability to decrease specific binding, was Gpp(NH)p greater than GTP greater than or equal to ITP greater than GDP greater than ATP greater than GMP greater than IDP. The kinetic alterations induced by a maximally effective concentration of Gpp(NH)p were: (a) a reduced steady state level of binding and (b) a markedly slower rate of ligand dissociation. The presence of Gpp(NH)p was found to increase the affinity of [125I]-angiotensin binding sites in rat renal cortex membranes. This contrasts with the decreases in affinity of [125I]-angiotensin binding reported in adrenal and mesenteric artery membranes.

Angiotensin II↗
PubMed1983

Sympathetic innervation of the jejunal villus.

Using fluorescent histochemical methods it has been shown that the noradrenergic nerves in the jejunal villus are associated with the capillaries underlying the basolateral membrane of the epithelium. Noradrenergic fibres were also seen to lie between the epithelial basolateral membrane and the capillaries but were never observed close to the epithelium unless accompanied by an underlying capillary. The distribution of noradrenergic fibres suggests that it is unlikely that noradrenaline diffuses directly from the varicosity to the epithelial basolateral membrane. Noradrenaline may, therefore, act on the capillary itself and in some way affect fluid absorption. However, noradrenaline released adjacent to a capillary might diffuse into the capillary to be distributed at another site along its course.

Animals↗
PubMed1983

The binding of [125I]-angiotensin to rat renal epithelial cell membranes.

1 Specific high affinity binding sites for [125I]-angiotensin II have been identified in crude basolateral and brush border membranes from rat cortex. 2 A central high affinity site, KD 0.62 nM; Bmax 299 fmol/mg was identified as part of a complex multicomponent binding system. 3 This high affinity site was saturable and exhibited specificity for angiotensin II analogues and closely related peptides but not for bradykinin, substance P or peptide fragments of angiotensin II. 4 Specific [125I]-angiotensin II binding was partially dependent on NaCl. Absence of NaCl resulted in a decrease in Bmax, had no effect on the rate of association but increased the rate of dissociation of [125I]-angiotensin from its binding site.

Alkaline Phosphatase↗
PubMed1983

Furosemide fails to alter plasma active or inactive renin in conscious sheep but does so in anaesthetized animals.

Regulation of plasma levels of active and inactive renin was investigated using sheep with indwelling artery, vein and bladder catheters. Control and experimental studies were carried out in the same animals on different days. Volume depletion during any single experiment was limited to a maximum of 50 ml. Despite large changes in sodium and water excretion, the diuretic furosemide at two dose levels, 1 and 10 mg/kg, failed to alter plasma levels of either active or inactive renin in conscious sheep. Induction of pentobarbitone anaesthesia in the sheep did not, per se, alter either plasma active or inactive renin. Furosemide (10 mg/kg) in anaesthetized animals produced a similar diuresis and natriuresis response to conscious sheep, but plasma active renin increased by 270% and inactive renin decreased to zero. In conscious sheep given an infusion of papaverine, furosemide also produced an increase in plasma active renin and a concurrent decrease in the inactive form. In both anaesthetized animals and in conscious sheep infused with papaverine, furosemide-induced intrarenal vasodilation, as evidenced by changes in clearance of p-aminohippuric acid, was much reduced in comparison to the conscious animals. This may be significant in relation to the control of renin secretion. It appears that the macula densa sodium receptor, which is considered to regulate renin release, will only function after it has been primed by other intra- or extrarenal factors. This is discussed, particularly in relation to the possible role played by the prostaglandin system.

Anesthesia, Intravenous↗
PubMed1983

Intestinal fluid absorption in spontaneously hypertensive rats.

A comparison has been made of intestinal fluid absorption between male Okamoto spontaneously hypertensive rats (s.h.r.) and normotensive male Wistar controls. S.h.r. show enhanced fluid absorption both in hypertensive adults and in young s.h.r. before hypertension has developed. Several potential causes for increased fluid transport in s.h.r. were tested using pharmacological antagonists. It is unlikely that enhanced fluid absorption is due to high sympathetic nervous activity, the renin-angiotensin system or is secondary to hypertension. Intestine from s.h.r. have a high short-circuit current indicating a change in ion pump activity. These results are discussed in relation to the possible causes of increased fluid (ion) transport by the intestine of s.h.r.

Animals↗
PubMed1983

Secretion control for active and inactive renin: effects of calcium and potassium on rabbit kidney cortex slices.

Release of active and inactive renin by rabbit kidney cortex slices was investigated. Inactive renin was estimated as the increase in renin activity after acidification (pH 2.8) of slice supernatant solutions. In Ca2+-free media, release of both active and inactive renin was increased but the changes in inactive renin were more marked. The percentage of total renin released which was inactive ranged from 8.3% ([Ca2+] = 9.2 mM) to 34.5% (zero [Ca2+]) with a linear relationship (r = -0.96) over the range of [Ca2+] studied. Depolarizing media ([K+] = 20 mM) suppressed release of inactive renin more than release of the active form. This effect, for both forms of renin, was lost when Ca2+ ions were omitted from the incubation media. This suggests that influx of Ca2+ ions was responsible for the reduced renin secretion following depolarization of the juxtaglomerular cells. Reducing the [K+] of the incubation buffer from 5.7 mM (control) to 1.0 mM did not alter active renin but increased release of inactive renin. Low [K+] media abolished the stimulatory effect of low [Ca2+] on release of both forms of renin. In incubation media with low [Ca2+] or with low [K+] the mixture of renins released by the kidney cortex slices correlated with that found in extracts of non-incubated kidney: that is, about 35% of the total renin was in the inactive form. Mechanisms controlling the secretion of active and inactive renins by the kidney are at least partially independent. Differential secretion of the two forms, perhaps linked to regulation of the activation of inactive renin before release, appears to be the basis of a control step in the over-all expression of the renin-angiotensin system. This may be coupled in some way to juxtaglomerular cell Na+ ion flux.

Animals↗
PubMed1982

The effects of thermal injury on gastrointestinal motor activity in the rat.

Gastrointestinal motor function was studied in conscious rats. The gastric emptying time, small intestinal motility and the colonic transit time were measured. A burn injury, covering about 15 per cent of the body surface area was applied to experimental animals; control animals received a mock burn. Burn injury caused a marked inhibition of gastrointestinal motility. This inhibition was significantly improved by a continuous saline infusion, but saline infusion alone had no effect on the gastrointestinal propulsive motility of normal rats.

Animals↗
PubMed1982

Active and inactive renin release from rabbit kidney cortex slices: effect of sodium concentration and of furosemide.

1. Active and inactive renin release by rabbit kidney cortex slices was investigated. Inactive renin was estimated as the increase in renin activity after acidification (pH 2 . 8) of slice supernatant solutions. 2. Active renin release was increased when incubation medium [Na+] was reduced. This relationship was linear (r2 = 0 . 96) over the range [Na+] = 23-133 mM. 3. For the same range of [Na+] inactive renin secretion decreased when medium [Na+] was reduced (r2 = 0 . 92). Therefore, the proportion of total renin which was in the inactive form decreased linearly as [Na+] was reduced (r2 = 0 . 97). 4. Chloride ions did not appear to be important in altering the secretion of either active or inactive renin. 5. Adding furosemide to the incubation medium in concentrations up to 40 micrograms/ml. did not change secretion of either form of renin. The action of furosemide on secretion of active and inactive renin in vivo is therefore secondary to altered renal function. 6. Regulation of the relative amount of active and inactive renin in plasma could be entirely an intrarenal event. It is not essential to invoke a plasma activating enzyme for inactive renin in order to explain changes in plasma levels of the two forms of renin. 7. This paper supports the hypothesis that release of inactive renin by the kidney is controlled by a sodium-sensitive mechanism.

Animals↗
PubMed1982

Secretion control for active and inactive renin: interactions with calcium and sodium ions.

Excitation-secretion coupling for active and inactive renin was investigated by manipulating the ionic composition of media in which rabbit kidney cortex slices were incubated. Alterations in [Ca++] and [K+] produced qualitatively similar, but quantitatively distinct, changes in the release of the two forms of renin. Under control conditions, the slices secreted 15-20% of total renin in the inactive form and exposure to Ca++-free or low [K+] media increased this to 30-40%, a similar proportion to that stored within the kidney. Decreasing [Na+] stimulated release of active renin but reduced inactive renin. There appeared to be antagonism between the effects of Na+ and Ca++ ions in respect of active renin but synergism for release of the inactive form. It is suggested that the characteristics of a single renin release mechanism in the rat kidney resemble those for secretion of inactive, rather than active, renin in other species.

Animals↗