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Biomedical subjects

J Hardcastle

Publications and source records attributed to J Hardcastle.

At least 73 records · Page 4Linked to original sources
PubMed1986

A comparison of some of the permeability characteristics of intact and tape-stripped hamster cheek pouches in vitro.

Cheek pouches were removed from anesthetized hamsters and were either tape-stripped or left intact and then mounted in Ussing chambers, where they were bathed in Krebs-Ringer bicarbonate saline. A potential difference could be measured across all pouches and was stable for over an hour across the unstripped pouches. The electrical resistance across the unstripped pouches was high (8960 omega.cm2), whereas the resistance across the tape-stripped pouches was significantly lower (p less than 0.01), suggesting that these pouches are likely to be more permeable than the unstripped pouches. Reflection coefficients of urea, ethanol, and glycerol were derived by means of streaming potentials. Values for intact pouches were all close to 1 and for tape-stripped pouches were 0.938, 0.822, and 0.509, respectively. Permeability coefficients for urea and ethanol across intact and tape-stripped pouches were, respectively, 12.5 X 10(-9)cm/min; 27.6 X 10(-9) cm/min; 2325 X 10(-9)cm/min; and 28471 X 10(-9) cm/min. The hamster cheek pouch has a high electrical resistance; it is an impermeable structure in which the keratin layer appears to provide a major barrier to the passage of water, ions, and certain solutes.

Animals↗
PubMed1986

Effect of auranofin on absorptive processes in the rat small bowel.

Mucosal auranofin (AF) caused a concentration dependent inhibition of fluid, Na+, glycine and galactose transport by everted sacs of rat small intestine (IC50 = 2 X 10(-4) M). Inhibition of nutrient absorption was not due to reduced fluid uptake since a similar reduction in fluid uptake induced by a mucosal osmotic load failed to alter glycine transport. Inhibitory effects of AF were not observed when metabolism was reduced, suggesting that carrier mediated entry processes were unaltered. AF inhibited Na+, K+-ATPase activity in isolated enterocytes (IC50 = 2 X 10(-4) M), without affecting Mg2+-dependent ATPase activity. Our studies suggest that the actions of AF on small intestinal absorption may result from inhibition of the Na+ pump.

Adenosine Triphosphatases↗
PubMed1986

Effect of auranofin (SK&F 39162) on water and electrolyte flux in canine small bowel: a possible diarrheogenic mechanism.

Auranofin (AF) a new antiarthritic gold compound effective when administered orally, frequently causes diarrhea with abnormal stool electrolyte content. Studies were designed to determine the mechanism of the diarrhea caused by AF. In perfused canine Thiry-Vella loops, AF caused significant elevations in effluent volume, osmolarity, and sodium concentration and a significant decrease in potassium concentration. In mucosal homogenates of rat small bowel, AF inhibited sodium, potassium ATPase in a concentration dependent manner. AF did not alter canine colonic smooth muscle activity in vitro. We suggest that AF induced diarrhea results from interruption of normal water and electrolyte absorption by inhibition of enterocyte sodium, potassium ATPase activity.

Animals↗
PubMed1985

The secretory action of barium chloride in rat colon.

BaCl2, applied serosally, caused a rise in the p.d. and short-circuit current (s.c.c), and a decrease in tissue resistance in stripped sheets of rat colon. This response was dose dependent. Mucosal application of BaCl2 was without effect. The BaCl2-induced rise in s.c.c. was inhibited by reducing the serosal Na+ concentration to 25 mM. Lowering the mucosal Na+ concentration was without effect. Ouabain (10(-3) M in serosal fluid) and furosemide (10(-3) M in serosal fluid) both reduced the rise in s.c.c. induced by BaCl2. Flux determinations indicated that BaCl2 inhibited Na+ absorption and stimulated Cl- secretion by the colon. In vivo, BaCl2 increased fluid accumulation within the colonic lumen, an effect that was associated with a rise in the transcolonic p.d. Increasing the serosal K+ concentration to 20 mM reduced the responses to BaCl2, acetylcholine and theophylline, and this could not be entirely accounted for by the concomitant reduction in the serosal Na+ concentration. As high serosal K+ did not mimic the secretory response it would appear that BaCl2 does not act by blocking K+ channels. The rise in s.c.c. induced by BaCl2 was not reduced by Ca2+-free conditions, but it was inhibited by 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) and trifluoperazine. BaCl2 did not alter cyclic AMP production by colonic scrapes. It is concluded that BaCl2 induces colonic secretion by the release of intracellular Ca2+, which then combines with calmodulin to activate the secretory process.

Action Potentials↗
PubMed1984

Effect of secoverine and atropine on intestinal secretion and motor activity in the rat small intestine in-vivo.

The actions of secoverine and atropine on bethanechol-induced intestinal secretion, hypermotility and transintestinal potential difference were investigated in the rat jejunum in-vivo. Both secoverine (10(-7) mol kg-1) and atropine (1.2 X 10(-9) mol kg-1) inhibited motility at doses that did not affect secretion or transintestinal potential difference. However, secoverine was a less potent antagonist of all the bethanechol-induced changes than atropine. Increases in transintestinal potential difference were more closely related to production of fluid secretion than to increases in motility.

Animals↗
PubMed1984

The action of R51619 on transport processes in the rat small intestine.

R51619, an agent reported to release endogenous acetylcholine, increased the potential difference and short-circuit current across non-stripped, but not stripped sheets of rat mid-intestine. The response was abolished by both hexamethonium and atropine. R51619 stimulated fluid accumulation by intestinal loops in-vivo suggesting its predominant effect is to stimulate anion secretion. These results are consistent with R51619 releasing endogenous acetylcholine within the myenteric plexus to activate postganglionic cholinergic fibres which stimulate intestinal secretion via muscarinic cholinoreceptors.

Animals↗
PubMed1984

The involvement of calcium in the intestinal response to secretagogues in the rat.

The involvement of Ca2+ in the regulation of intestinal secretion was investigated in stripped sheets of rat mid-intestine. Removal of serosal Ca2+ together with the addition of EGTA at concentrations of 0.5 and 1 mM inhibited the rise in short-circuit current (s.c.c.) induced by both acetylcholine and theophylline, a similar degree of inhibition being observed with both secretagogues. Ca2+-free serosal fluid with 0.5 mM-EGTA added reduced significantly the rises in s.c.c. induced by A23187, acetylcholine, 5-hydroxytryptamine, theophylline, dibutyryl cyclic AMP and prostaglandin E2, but not the increased s.c.c. associated with glucose absorption. The Ca2+ channel blocker verapamil produced similar results. The calmodulin antagonist trifluoperazine inhibited secretagogue action while its sulphoxide derivative was without effect at the same concentration. The intracellular Ca2+ antagonist TMB-8 reduced the increased s.c.c. observed with acetylcholine and dibutyryl cyclic AMP. The net Cl- secretion, but not the decreased mucosal-to-serosal Na+ flux, induced by acetylcholine was abolished in Ca2+-free conditions. There was no consistent effect on the reduction in the residual ion flux caused by acetylcholine. Absence of Ca2+ converted the stimulation of Cl- secretion induced by dibutyryl cyclic AMP observed under control conditions to an enhancement of net Na+ and Cl- absorption. It is concluded that intestinal secretagogues, whether they act through cyclic AMP or not, require both internal and external sources of Ca2+ if they are to produce their full effects. Moreover, it appears that the nature of the response to dibutyryl cyclic AMP depends on the prevailing Ca2+ concentration.

Acetylcholine↗
PubMed1983

The effect of barium chloride on intestinal secretion in the rat.

The addition of BaCl2 to the serosal solution, at concentrations from 0 X 25 mM to 10 mM, caused increases in potential difference, short-circuit current and resistance across stripped sheets of rat mid-intestine, although mucosal application had little effect. The response to BaCl2 was significantly greater than that obtained with the same concentration of CaCl2. An increase in net Cl- secretion entirely accounted for the rise in short-circuit current induced by BaCl2. BaCl2 inhibited net fluid uptake by everted sacs. It also enhanced the accumulation of fluid by intestinal loops in vivo and this was associated with an increased potential difference. The response to BaCl2 in vitro was not reduced in the absence of serosal Ca2+ ions. The effect of BaCl2 was abolished by trifluoperazine and also by TMB-8 (8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride). BaCl2 did not alter cyclic AMP production by isolated enterocytes. It is concluded that BaCl2 induces intestinal secretion by releasing Ca2+ from intracellular stores which then combines with calmodulin to stimulate the secretory process.

Animals↗
PubMed1981

The action of loperamide in inhibiting prostaglandin-induced intestinal secretion in the rat.

1 The mechanisms by which loperamide inhibits the intestinal secretion induced by prostaglandin E2 were investigated in rat jejunum. 2 In vivo loperamide prevented prostaglandin-induced fluid secretion but did not reduce the associated rise in the transintestinal potential difference. 3 In intestinal sheets the electrical response to prostaglandin E2 was enhanced in the presence of loperamide. 4 The ionic basis of these changes was determined by measuring Na+ and Cl- fluxes across intestinal sheets. Loperamide did not reduce the prostaglandin-induced increase in net Cl- secretion, although it prevented the inhibition of mucosal-to-serosal Na+ movement. 5 Loperamide does not alter cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels by a direct action at the enterocyte, since in isolated enterocytes neither basal nor prostaglandin-stimulated cyclic AMP levels were affected by the drug.

Animals↗
PubMed1981

Action of 5-hydroxytryptamine on intestinal ion transport in the rat.

1. 5-HT increased the electrical activity of rat jejunum both in vivo and in vitro. The increased potential difference and short-circuit current resulted from a stimulation of electrogenic chloride secretion. NaCl absorption may also have been inhibited. 2. 5-HT did not alter cyclic AMP levels in isolated enterocytes. 3. The 5-HT response in vivo was unaffected by atropine, cyproheptadine, propranolol and hexamethonium. Phenoxybenzamine reduced the maximum response without affecting the dose required to produce a 50% maximum response. Methysergide, at a dose of 40 mg/kg, had a similar effect while a lower dose of 2 mg/kg produced no change. Mianserin competitively antagonized the response to 5-HT, a dose of 2 mg/kg producing a fourfold increase in the amount of 5-HT required to produce a 50% maximum response. 4. Acetylcholine and 5-HT seem to act independently in inducing intestinal secretion since atropine did not block the response to 5-HT and Mianserin did not alter the response to acetylcholine. 5. Experiments in which the intestinal villi or crypts were subjected to preferential damage suggested that 5-HT primarily produced its response at the crypt cell level.

Animals↗
PubMed1978

The effect of bradykinin on the electrical activity of rat jejunum.

Bradykinin increased the potential difference across both the jejunum and colon of the rat. This effect was significantly reduced by indomethacin, suggesting that it was mediated by prostaglandins. The possibility that bradykinin may contribute to the diarrhoea of the carcinoid syndrome by inducing a net secretory state in the intestine is discussed.

Animals↗
PubMed1978

Localization of the effect of acetylcholine in regulating intestinal ion transport.

1. The location of the site involved in the secretory response of rat jejunum and colon to ACh was investigated by selectively damaging either the villi of the jejunum and the surface epithelium of the colon or the crypts. 2. The secretory response induced by ACh was measured both in terms of changes in electrical activity and chloride fluxes. 3. Exposure of the mucosa to 2 M-Na2SO4 for 30 min selectively damaged the jejunal villi and colonic surface epithelium but did not reduce the increased potential difference and current generated by ACh. 4. When resistance changes were taken into account the colonic response was markedly increased after Na2SO4 treatment although the jejunal response was unchanged. Under control conditions ACh reduced net Na absorption and stimulated Cl secretion by the colon. After exposure to Na2SO4 only the Cl secretory component of the ACh response remained, thus accounting for the enhanced effect. 5. Cycloheximide, administered I.V. at a dose of 12 mg/kg, damaged the crypts after 2 hr without affecting the villi of the jejunum or the surface epithelium of the colon. After cycloheximide treatment the increased potential difference, current and net Cl secretion induced by ACh were significantly reduced. 6. The crypts therefore appear to be the site primarily involved in the secretory response of rat jejunum and colon to ACh, although in the colon an inhibitory effect on the Na transport process located in the surface epithelium was observed.

Acetylcholine↗
PubMed1978

Effect of actively transported hexoses on afferent nerve discharge from rat small intestine.

1. The afferent discharge of mesenteric nerves has been recorded while perfusing salines of different composition through the lumen of rat ileum. The p.d. across the ileum and hexose absorption have also been measured. 2. The ileal mesenteric nerves were sensitive to actively transported hexoses. The discharge recorded increased dramatically on perfusion with 10 or 50 mM-glucose, quietening within 3 min of returning to glucose-free saline. A similar response was obtained with galactose. 3. No change in afferent discharge could be detected on perfusion of mannitol or the slowly transferred hexose, mannose. It is concluded that the response to glucose and galactose is not dependent on the stimulation of non-specific luminal osmoreceptors. 4. Phlorhizin prevented glucose from increasing the afferent nerve discharge. Subsequent perfusion with saline removed the phlorhizin and an afferent nerve response to glucose was restored. It is concluded that this response requires glucose transfer beyond the phlorhizin-sensitive glucose entry mechanism at the luminal side of the mucosal epithelial cell. 5. Very small amounts of glucose or galactose were absorbed under the conditions employed. The time course for the change in p.d. correlated well with that described for the alteration in afferent nerve discharge. 6. Electron micrographs show that ileal nerves consist of bundles of small non-myelinated fibres of approximately 1 micron diameter. 7. The significance of the findings is discussed remembering that carbohydrate absorption is considered to be completed normally in the jejunum.

Action Potentials↗
PubMed1977

The role of acetylcholine in the regulation of ion transport by rat colon mucosa.

1. Acetylcholine increases the potential difference across rat proximal colon both in vivo and in vitro.2. There is a sigmoid relationship between the change in potential difference and the logarithm of the dose of acetylcholine. The dose-response curve is shifted to the left by neostigmine and to the right by atropine, suggesting that the action of acetylcholine is mediated by a muscarinic type of receptor.3. The dose-response curve for acetylcholine in vivo is not altered by the ganglion-blocking agents hexamethonium and pentolinium, suggesting a direct effect of this transmitter on the colon.4. Acetylcholine causes an increase in potential difference, a small decrease in resistance and hence a rise in the current generated by both normal and stripped everted sacs of rat colon.5. In the absence of sodium, the calculated current change produced by acetylcholine is reduced, and the removal of chloride has a similar inhibitory effect. The absence of bicarbonate does not significantly affect the response.6. Acetylcholine virtually abolished net sodium movement and induced net chloride secretion and these changes accounted for the increased short-circuit current.7. Acetylcholine had no effect on oxygen consumption by rings of colon.8. Tracts staining for acetylcholinesterase were observed running from the submucous plexus towards the mucosal epithelium.9. This study shows that acetylcholine can influence ion movement by rat colonic mucosa and suggests that the autonomic nervous system might be involved in the regulation of transport mechanisms in this tissue.

Acetylcholine↗