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T Scratcherd

Publications and source records attributed to T Scratcherd.

17 recordsLinked to original sources

Reflex co-ordination of corporal and antral contractions in the conscious dog.

This study characterizes the role of extrinsic nerves in the co-ordination of corporal and antral contractions in the dog. Fasting motor activity was recorded in conscious dogs with stomachs previously divided into separate corporal and antral pouches. Both corpus and antrum showed synchronized phases of activity and quiescence recognizable as migrating motor complexes (MMCs, duration 81.2 +/- 9.6 min, n = 4). Moreover, individual contractions were temporally linked such that corpus contractions, occurring at 76 +/- 4 s intervals, were each followed by a burst of one to three antral contractions at a frequency of 4-5 min-1. The mean latency between the onset of individual contractions in the corpus and antrum was 10.9 +/- 2.6 s (n = 4). Denervation of the antral pouch in two additional dogs did not affect the MMC cycle (mean durations 106.6 and 82.1 min) and the onset of activity in the corpus and antrum was generally co-ordinated but less precise. However, individual antral contractions were no longer linked to corporal contractions, occurring randomly throughout the corpus contraction cycle. This was associated with a lower contraction frequency in the denervated antral pouches than in the corpus (0.3 +/- 0.1 min-1 compared to 0.6 +/- 0.08 min-1). It is proposed that a vagal reflex, excited by corporal tension receptors, provides phasic excitation facilitating the generation of antral contractions. Such a reflex is likely to reinforce the myogenic mechanisms which occur in the intact stomach and thus plays a role in co-ordinating gastric peristalsis.

Animals

Pre-pyloric mechanisms regulating gastric motor function in the conscious dog.

Reflex mechanisms regulating gastric motor function were studied in four conscious dogs, whose stomachs had been surgically divided into separate corporal and antral pouches. Interactions between the corpus and antrum were investigated in fasted animals by balloon distension of each region. During the quiescent phase (phase I) of the migrating motor complex (MMC), distending the corpus with volumes greater than 80 ml resulted in contractions of the corpus, which persisted for as long as the distending stimulus was applied. This corporal distension also initiated antral contractions which were greater if the antrum was moderately distended and also greater with a larger corporal distending volume up to 300 ml. Graded 5 ml inflation of the antrum during the quiescent phase of the MMC stimulated antral contractions. This antral response to antral distension was augmented when the corpus was inflated but was only statistically significant with antral volumes below 25 ml. Distension of the antrum with volumes greater than 12.5 ml caused inhibition of corporal contractions during both the active phase of a migrating complex or when stimulated by corporal inflation. The degree of inhibition was proportional to the distending stimulus and was present for the duration of the applied distension. For antral volumes of 50 ml the inhibition persisted for a variable time after the stimulus was withdrawn. The inhibition of corporal activity by antral distension was still effective after blocking acid secretion with cimetidine (100 mg), which would eliminate spillage of acid into the jejunum as a cause of the inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Involvement of gastrointestinal mechano- and intestinal chemoreceptors in vagal reflexes: an electrophysiological study.

The role of gastrointestinal mechanoreceptors and intestinal chemoreceptors in the genesis of vago-vagal reflexes was assessed by recording single vagal efferent fibre discharge in the urethane-anaesthetized ferret during procedures known to activate discrete populations of gastrointestinal afferent fibres. Distension of the stomach, duodenum and jejunum was used to activate mechanoreceptors while perfusion of the intestinal loops with various chemical solutions was used to activate mucosal chemoreceptors. Mechanical stimulation of the stomach and/or intestine was effective in modulating vagal efferent discharge in 90% of units tested. The response (either excitation or inhibition of efferent firing) was characterized by its short-latency (less than 1 s), slow-adaptation, and rapid return on removal of the stimulus. In contrast, chemical stimulation was much less potent evoking clear-cut responses in only 26 of the 109 efferent units. Luminal HCl was the most effective stimulus accounting for 81% of the efferent responses although these were of long-latency (greater than 1 min), gradual in onset and poorly maintained. Other efferent responses to HCl and hypertonic saline were characterized by a long-latency, sudden increase in discharge associated with the prodrome of vomiting. We conclude that while the mechanosensitive afferent input is well represented in terms of the genesis of vagal reflexes, the chemosensitive afferent input may be more important in behavioural aspects of visceral stimuli like vomiting.

Animals

Disruption of the jejunal migrating motor complex by gastric distension and feeding in the dog.

1. The jejunal motor response to gastric distension has been quantified in the conscious dog and compared with that of feeding in order to determine the role of the physical bulk of a meal in the conversion from fasted to fed motor activity. 2. In six dogs gastric distension abolished the cyclical migrating motor complex (m.m.c.) and evoked a pattern of continuous irregular jejunal motility similar to that seen postprandially, but only after a latency of 21.5 +/- 2.7 min compared to that of 7.1 +/- 1.2 min for the response to feeding. Computer analysis of distension and fed jejunal motility revealed similar distributions of intervals between contractions and contraction amplitudes with comparable mean values for both. 3. In two dogs with antrum and corpus surgically divided distension of the corpus had a similar effect on jejunal motility although the latency to both distension and feeding were considerably less. 4. By varying the period of distension it has been possible to control accurately the duration of the jejunal motor response and so assess its effectiveness in disrupting the timing of the m.m.c. The return to m.m.c. cycling following deflation was independent of preceding complexes. The occurrence of the post-distension activity front was closely related to the act of deflation itself (R = 0.94) following a latency of 26.2 +/- 2.1 min (n = 39). 5. It is concluded that the bulk of a meal contributes significantly to the early part of postprandial motility and is capable of disrupting the timing of subsequent migrating motor complexes.

Animals

A permissive role for the vagus nerves in the genesis of antro-antral reflexes in the anaesthetized ferret.

1. The role of the vagus nerves in the genesis of antro-antral reflexes was investigated in the urethane-anaesthetized, splanchnectomized ferret. 2. Antral distension stimulated antral contractions with a threshold volume of 3.5 +/- 0.9 ml (corresponding to an intra-antral pressure of 0.27 +/- 0.11 kPa) by a vagal-dependent mechanism as indicated by the attenuated response seen during vagal blockade by cooling. Atropine (1 mg/kg) abolished the antral response to distension. 3. In vagotomized animals, close arterial infusions of acetylcholine at a dose sufficient to return antral motility to basal levels led to the reappearance of the reflex. Low-frequency electrical stimulation of the preganglionic vagal neurones had a similar effect. These effects were also abolished by atropine (1 mg/kg). 4. Hexamethonium (10-25 mg/kg) suppressed the potentiating effect of acetylcholine, indicating a ganglionic site of action. The attenuated response to antral distension seen in vagotomized animals in the absence of exogenous acetylcholine or electrical vagal stimulation was not sensitive to hexamethonium but abolished by atropine (1 mg/kg). 5. The results are consistent with the vagus performing a permissive role in the genesis of antro-antral reflexes mediated through local enteric pathways.

Acetylcholine

Electrolyte secretion by the isolated cat pancreas during replacement of extracellular bicarbonate by organic anions and chloride by inorganic anions.

1. The effect of replacing extracellular bicarbonate and chloride by other anions on the volume and composition of secretin-stimulated pancreatic juice has been analysed in the isolated, perfused cat pancreas. 2. The anions of some aliphatic carboxylic acids were able partially to substitute for bicarbonate in sustaining pancreatic secretion. The order of effectiveness was: acetate greater than proprionate greater than butyrate greater than formate. 3. The rate of secretion in the presence of 25 mM-acetate was 42% of that achieved with 25 mM-bicarbonate. The concentration of acetate in the secretion varied with flow rate, reaching a maximum of 120 mM at high flow rates and declining at lower flow rates, with reciprocal changes in chloride concentration. Bicarbonate was always present in the secretion at a concentration of 5--7 mM. 4. Inorganic anions were able totally or partially to substitute for chloride in sustaining secretion. In relation to chloride, their degree of effectiveness was: chloride = bromide = or greater than nitrate greater than iodide greater than sulphate greater than methyl sulphate greater than isethionate. Those anions which had no effect on secretion rate (i.e. bromide and nitrate) also had no effect on the bicarbonate concentration of the secretion and themselves appeared in the secretion in place of chloride. Those anions which inhibited secretion increased the bicarbonate concentration in the secretion in proportion to the degree of inhibition they caused (i.e. the increase was greatest with isethionate). 5. When perfusate chloride was only partially replaced by bromide or iodide the ratios of chloride: bromide and chloride: iodide in the secretion were approximately equal to those in the perfusate. 6. The carbonic anhydrase inhibitor acetazolamide reduced secretory rate and bicarbonate concentration when added to normal perfusion fluid or chloride-substituted fluids, but had no effect following replacement of perfusate bicarbonate by acetate. 7. These observations illustrate that an extracellular source of permeant anions is required for optimal pancreatic bicarbonate secretion to occur. This may indicate the participation of an anion exchange carrier in the transport events responsible for this secretory process.

Acetazolamide

The permeability of the secretin stimulated exocrine pancreas to non-electrolytes.

1. A method of measuring the permeability of the pancreas by determining the apparent reflexion coefficient (sigmaA) is described, in the isolated pancreas secreting maximally under the influence of secretin. The principle is to add a non-electrolyte to the perfusate which will create an osmotic gradient (RTsigmadeltaC) counter to that of active transport and reduce the secretion rate. This is compared with the effect of an equal concentration (0.1 M) of sucrose (RTdeltaC; sigma = 1). The apparent reflection coefficient is obtained by dividing the percentage reduction in the secretion rate due to the test molecule with that due to sucrose. 2. Sucrose when added to the perfusate inhibits pancreatic secretion. For every 10 mM increase in sucrose concentration, the secretion rate was inhibited by 7.1%. It has been estimated that an osmotic gradient of 131 m-osmole/kg water will cause zero flow rate. This is a measure of the pressure required to counteract the local osmotic gradient set up by active transport, it is equivalent to about 3.4 atm. 3. Non-electrolytes with molecular volumes greater than about 85 cm3 mole-1 are relatively impermeable, below this value they enter the pancreatic juice with increasing ease as the molecular volume decreases. 4. SigmaA for a number of compounds has been measured: urea 0.17; ethanediol 0.27; thiourea 0.51; glycerol 0.69; creatinine 0.81; erythritol 0.91; arabinose 0.96; xylose 0.98; sorbitol 0.98. 5. The addition of non-electrolytes to the perfusate had effects on pancreatic secretion which were a function of sigmaA. For molecules with sigmaA lying between 0.81 and 1.0 an osmotic load of 0.1 M increased both the concentration of sodium plus potassium and the concentration of chloride plus bicarbonate by about 50 m-mole/l. Whereas the cation change is almost exclusively one of sodium that of the anions was preferentially an increase in chloride. For compounds with sigmaA lying between 0 and 0.81 the concentration of sodium plus potassium was proportional to sigmaA. 6. A number of compounds have been described which inhibit pancreatic secretion, other than by an osmotic effect. These include acetaldehyde, thioglycerol, nicotinamide, ribose, dihydroxyacetone, and glyceraldehyde. 7. It is concluded that the pancreas is more permeable than the gall-bladder of rabbit, fish and bullfrog, the proximal tubule of the kidney of rat and the small intestine of bullfrog, but is probably similar to that of small intestine of guinea-pig and man.

Animals

The effects of alloxanate, nicotinic acid and imidazole on secretory processes and the activities of adenylate cyclase and 3',5'-AMP phosphodiesterase in cat pancreas.

1 Nicotinic acid and alloxanate inhibited water and electrolyte secretion in a dose-dependent fashion when added to the perfusate of the isolated saline-perfused pancreas of the cat stimulated by a supramaximal dose of secretin.2 There were no changes in the concentration of sodium or potassium secreted into the juice, but the anions exhibited changes which were related to flow rate. As the flow rate declined the chloride concentration increased with a reciprocal decrease in bicarbonate concentration.3 Nicotinic acid and alloxanate inhibited enzyme secretion stimulated by carbachol.4 Imidazole inhibited pancreatic electrolyte secretion, but stimulated amylase secretion. Atropine (0.14 muM) reduced the secretion of amylase but did not abolish the effect.5 Adenylate cyclase prepared from cat pancreas, was stimulated by the octapeptide of cholecystokinin-pancreozymin, secretin and sodium fluoride.6 Alloxanate strongly inhibited both basal and hormone-stimulated adenylate cyclase activity. Nicotinic acid and imidazole stimulated basal adenylate cyclase activity but had little effect on secretin-stimulated activity.7 Alloxanate, nicotinic acid and imidazole were all without effect on phosphodiesterase when tested in the presence of micromolar concentrations of adenosine 3',5'-monophosphate (cyclic AMP). At higher cyclic AMP concentrations (2 mM) alloxanate and nicotinic acid were without effect, whereas imidazole had a slight stimulatory effect at 10 mM which was more marked at 50 mM.8 Alloxanate (10 mM) strongly inhibited both basal and secretin-stimulated adenylate cyclase activity.9 It is concluded that the effects of nicotinic acid, alloxanate and imidazole on pancreatic secretion are not mediated entirely through their effects on the adenylate cyclase or phosphodiesterase enzyme systems.

3',5'-Cyclic-AMP Phosphodiesterases

A sensitive method for the biological assay of secretin and substances with "secretin-like" activity in tissues and biological fluids.

The isolated perfused pancreas is extremely sensitive to secretin and can be used to assay very small quantities of secretin. The addition of theophylline to the perfusate increases the sensitivity of the preparation 4 to 10 fold so that in a good preparation as little a 0.001 C.U. may be detected. Secretin-like activity was detected in biopsy samples of jejunal mucosa taken perorally from man, in the blood of some patients suffering from a profuse watery diarrhoea, and in a metastatic tumour obtained from one such patient. It was also observed that 1 clinical unit of secretin was equal to 4.4 Crick, Harper, Raper units.

Adult