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1. The secretion rate of bicarbonate by the isolated saline‐perfused cat pancreas was linearly related to the bicarbonate concentration of the arterial inflow at constant PCO2 and at high volume rates of secretion. 2. Pancreatic bicarbonate secretion was independent of arterial inflow pH at constant bicarbonate concentrations when the pH was manipulated by alterations in the PCO2 at high volume rates of secretion. 3. A small but statistically significant linear relationship existed between the pH of the arterial inflow and bicarbonate secretion at constant PCO2 after inhibition of carbonic anhydrase by acetazolamide. Under the same conditions no relationship was found between bicarbonate secretion and arterial inflow pH when the perfusate bicarbonate concentration was kept constant and the PCO2 varied. 4. When the volume rate of secretion was reduced by about 60‐70% of maximum no relationship was found to exist between arterial inflow pH and bicarbonate secretion at constant bicarbonate concentration in the perfusate. There was also no relationship between inflow pH and bicarbonate secretion at constant PCO2 down to a pH of 7.3 until the bicarbonate concentration of the perfusate was reduced below 10 mM, when the secretion rate fell off rapidly. 5. A linear relationship was found to exist between the volume rate of secretion and the PCO2 of the pancreatic juice and the output of lactate both in the isolated saline‐perfused gland and the blood‐perfused pancreas in situ. 6. At high rates of secretion the PCO2 of the pancreatic juice was always higher than that of either the arterial inflow or the venous outflow. There is therefore no gradient for the passive movement of carbon dioxide between the arterial inflow and the pancreatic juice. 7. Inhibition of secretion with acetazolamide caused a fall in the PCO2 of pancreatic juice and increased the output of lactate. The secretion of lactate was not due to hypoxia as it also occurred in the blood‐perfused gland in situ which had normal haemoglobin concentrations and oxygen saturation. 8. It is concluded that the secretion of bicarbonate is independent of arterial pH but critically dependent upon the arterial concentration of the bicarbonate ion. These experiments do not support the concept that the secretion of protons over the basolateral membrane is the major primary event in pancreatic secretion of bicarbonate.

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.

1. The secretion of sodium, potassium and lithium has been studied in the isolated cat pancreas, perfused with bicarbonate buffered saline solutions of varying composition and osmolality, and stimulated maximally with secretin.

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.

1. The effect of electrical stimulation of the vagus nerve with different patterns of impulses (the total number of stimuli remaining constant) on gastric acid secretion and gastric motility were investigated in the anaesthetized ferret. Three stimulus patterns were used: continuous, bursts at ten times the continuous frequency but for a tenth of the time, and a natural burst pattern obtained from a recording of vagal efferent fibre discharge. 2. The natural burst pattern gave rise to gastric contractions of larger amplitude than either the artificial burst or continuous stimulation, while continuous stimulation gave rise to larger changes in tonus. Acid secretion, however, was reduced by the natural pattern of stimulation as compared to the output during continuous stimulation, but to a lesser extent than that due to artificial burst stimulation. 3. Burst stimulation at 10 impulses/sec resulted in a larger output of acid and greater amplitude of gastric contraction than the equivalent continuous stimulation. This potentiation was lost at stimulation frequencies above 30 impulses/sec. 4. At burst frequencies of 60 and 120 impulses/sec there was a marked reduction in acid output and amplitude of contraction as compared with continuous stimulation at 6 and 12 impulses/sec respectively. 5. These results are discussed in relation to the functional significance of the different patterns of vagal discharge seen in the anaesthetized ferret.

Cooling the cervical vagi of the anaesthetized splanchnectomized cat to 2 degrees C caused a 54.4 +/‐ 8.8% inhibition of pancreatic electrolyte secretion stimulated submaximally with pure secretin. On rewarming the vagi there was a prolonged increase in secretion rate over and above the control rate which existed before cooling. The increase lasted about 90 min. There were no changes in acid/base status due to interference of the lung inflation reflex which could account for the inhibition of secretion and the subsequent rebound. Cold block of the cervical vagi increased the transpancreatic electrical conductance, indicating that vasodilation had occurred and therefore eliminated a vasomotor cause for the inhibition. Electrolyte secretion was also inhibited by bilateral vagal section. Atropine only partially prevented the inhibitory response to vagal cooling. A cholinergic mechanism, therefore, accounted for some but not all of the response to vagal cooling. It is concluded that even in the fasted, anaesthetized animal vagal impulses facilitate the action of secretin on the pancreas. This facilitation is only partially cholinergic; the major part of the response is due to some non‐cholinergic transmitter substance. Such a mechanism may be necessary to potentiate the action of the very small amounts of secretin which appear to be released during a meal.

The effect of D‐ and L‐isomers of tryptophan and phenylalanine on fasting motor activity of canine jejunum were investigated. Only L‐tryptophan had any effect on jejunal motility. The concentration of L‐tryptophan required to elicit a motor effect in 50% of animals was estimated at 28 mM. 50 mM‐L‐tryptophan stimulated jejunal motility after a latency of 4.5 +/‐ 0.7 min. The pattern of motility was similar to that evoked by feeding but continued for only 41 +/‐ 5 min and failed to disrupt the normal timing of the interdigestive migrating motor complex (m.m.c.). The duration of the subsequent phase II of the complex was, however, significantly reduced. Multiple infusion of L‐tryptophan also failed to disrupt the timing of the m.m.c. These data are consistent with the hypothesis that specific breakdown components of protein digestion are implicated in the stimulation of postprandial motor activity. The mechanisms involved in the motor response to L‐tryptophan are discussed.

1. Enzyme secretion in response to short duration vagal stimulation or to rapid I.V.injections of cholecystokinin‐pancreozymin (CCK‐PZ) or gastrin or to intra‐arterial injections of acetylcholine is a function of the volume of juice secreted and not primarily a function of time.

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.

1. The rate and volume of gastric filling was estimated in conscious ferrets by measuring the amount of milk they would drink after an overnight fast. The mean volume was 94.5 +/‐ 7.5 ml. at a rate of 13.0 +/‐ 0.74 ml./min. An intragastric infusion rate of 10 ml./min to a total of 50 ml. was selected as a standard distension stimulus. 2. Action potentials were recorded from single gastric afferent fibres in the cervical vagus. All but two of thirty‐six afferent units were tonically active when the stomach was deflated. 3. Afferent fibres arising from receptors in the antrum showed modulation in phase with spontaneously occurring antral contractions. Afferent fibres from the corpus and fundus, however, discharged at irregular rates between 0.35 and 7.5 Hz with no correlation with the intragastric pressure rises associated with the antral contractions. 4. Inflation of the stomach with 50 ml. 0.9% NaCl at a rate of 10 ml./min stimulated antral motility and the rhythmic afferent discharge from the antrum was enhanced Receptors in the corpus and fundus increased their rate of discharge with increasing gastric volumes. Receptors in the region between the antrum and the corpus had the property of both types so that they responded to both distension and contractions. 5. On distension with 0.9% NaCl, fluid is distributed unevenly in the stomach. 80% was accommodated in the corpus and fundus, the remainder of the fluid entering the antrum. 6. The tension was measured in strips of stomach wall taken from corpus and antrum. For equal increments of stretch the development of tension was greater in the antral than in corpus strips. This physical property together with neurally mediated receptive relaxation of the corpus is the reason for the fluid distribution described above. 7. It is concluded that the properties of the tension receptor are determined by their site in the stomach. Those in the body and fundus signal the degree of distension and those in the antrum signal information concerning the amplitude, rate and duration of antral contractions.

1. In the urethane anaesthetized ferret gastric inflation with 50 ml. 0.9% NaCl at a rate of 10 ml./min evoked large gastric contractions. The threshold of intragastric pressure required to elicit the reflex was 3.1 +/‐ 0.5 cmH2O. 2. The response was enhanced by splanchnic nerve section and markedly reduced by bilateral cervical vagotomy, indicating that both afferent and efferent limbs of the reflex were in the vagus nerves. 3. By using a transected stomach it was shown that distension of the corpus evoked contractions of the antrum that were abolished by vagotomy. 4. The reflex activation of antral motility by vagal afferents with receptive fields in the corpus may play a physiological role in gastric emptying.

1. Under urethane anaesthesia the ferret has a stomach which exhibited spontaneous contractions. The amplitude of the contractions was reduced, but never abolished, by vagotomy, atropine or hexamethonium. 2. Electrical stimulation of the cut peripheral end of the cervical or abdominal vagus nerves activated both excitatory and inhibitory fibres, whereas reflex activation by stomach distension or by cytoglucopenia was predominantly excitatory on gastric motility. The magnitude of the response to electrical stimulation was dependent upon the stimulus frequency, duration and voltage. Stimulation for periods longer than 10 sec at 10 Hz caused an increase in tone and motility which declined almost to control values if it was sufficiently prolonged. 3. Short duration stimulation, 10 sec or less, at 10 Hz produced a single gastric contraction. An identical response could only be produced if a period of rest from 30 to 120 sec separated two such stimuli. 4. The frequency of gastric contractions was independent of the frequency of nerve stimulation. 5. Using a divided stomach, vagal non‐cholinergic, non‐adrenergic fibres were shown to cause mainly relaxation of the corpus region. Similar fibres supplied the antrum and their activation caused inhibition of spontaneous contractions. The transmitter may be ‘purinergic’ as rebound contractions were observed.

1. A single‐fibre‐dissection technique was used to investigate the reflex modulation of vagal efferent fibre discharge by afferent fibres from various parts of the gastrointestinal tract of the urethane‐anaesthetized ferret. 2. All but four of the 168 efferent fibres isolated in this study were spontaneously active. The majority of these had discharge frequencies of less than 6 spikes/sec. 3. All the efferent units received an afferent input from mechanoreceptors in the stomach. Two main types of response to gastric distension were seen: (i) an increase in efferent discharge and (ii) a decrease or complete suppression of efferent discharge. 4. The vagal efferent discharge was also modulated by duodenal and colonic distension, with the major effect being one of inhibition. 5. Bilateral vagotomy completely abolished the response to gastric distension in 68% of the units tested. The response to colonic and duodenal distension, however, was relatively unaffected by vagotomy. Thus the vagus provides the major afferent pathway from the stomach to these vagal efferent fibres, whilst the major input from the duodenum and colon is via a non‐vagal pathway. Both vagal and splanchnic afferents therefore converge on to the vagal nucleus. 6. The destinations of these vagal efferent fibres and their possible functions are discussed.

Spontaneous jejunal motility in the urethane‐anaesthetized ferret shows a cyclical pattern of contraction bursts alternating with quiescent periods described as ‘minute rhythm’ in conscious animals. Cooling the cervical vagi to below 4 degrees C or acute vagotomy abolished this pattern of motility. On re‐warming the vagi there was a return to cyclical motility after a latency which depended upon the contractile state at the time vagal conduction was restored. Electrical vagal stimulation produced bursts of contractions at the same frequency as the spontaneous motility. Longer periods of stimulation gave rise to bursts of contractions interrupted by periods of relative quiescence, mimicking the spontaneous motility, despite the continuous stimulation. Following atropinization all spontaneous motility was abolished, but electrical stimulation of the vagi revealed a non‐cholinergic, non‐adrenergic response whose characteristics differed from that of the cholinergic response. It is concluded that the vagus plays a permissive role in regulating the jejunal ‘minute rhythm’ via a cholinergic pathway and that there is a second excitatory vagal pathway which innervates non‐cholinergic post‐ganglionic neurones whose functional significance and transmitter mechanism is unknown.

Spontaneous colonic motility in the urethane‐anaesthetized ferret consists of two distinct types of contraction which correspond to the patterns recorded myoelectrically in conscious animals. This motility was abolished or greatly reduced when nervous conduction was prevented in the cervical vagi by cooling to below 4 degrees C. On rewarming the nerves the colonic motility returned, after a short latency, to the pre‐cool level. Atropine transiently abolished colonic motility. On its return the motility was significantly reduced but still sensitive to vagal integrity. Thus the atropine‐resistant colonic motility was also abolished or markedly reduced by cooling the cervical vagi to below 4 degrees C. On rewarming there was a longer latency for the return of motility compared to that before atropinization. Electrical vagal stimulation produced, after a short latency, large‐amplitude colonic contractions. Following atropine, the short‐latency response to electrical vagal stimulation was replaced in the majority of animals by a long‐latency response whose characteristics were quite different from those of the cholinergic response. These results are consistent with the vagus containing two functional motor pathways to the colon, one to cholinergic post‐ganglionic neurones and the other operating via a non‐cholinergic mechanism.

The continuous infusion of noradrenaline into the arterial supply of the isolated saline‐perfused pancreas caused a dose‐dependent rise in perfusion pressure, a reduction in perfusion rate and an inhibition of pancreatic secretion. With increasing dose there was always a greater reduction in secretion rate than there was of perfusate flow rate. Manual reduction of the perfusion rate resulted in a reduction in secretion rate. When noradrenaline reduced the perfusate flow by 44.2 +/‐ 6.0% the secretion rate fell by 76.6 +/‐ 14.1%. Manual reduction of the perfusion flow rate by a similar amount (43.0 +/‐ 5.7%) only reduced the secretion rate by 41.4 +/‐ 7.0%. The infusion of noradrenaline, when all calcium had been removed from the perfusate, caused only a small increase in perfusion pressure with little change in the perfusion flow whilst at the same time the inhibition of electrolyte secretion was relatively unaffected. The vasomotor and secretory effects of noradrenaline were abolished by phentolamine. It is concluded that noradrenaline inhibits pancreatic electrolyte secretion by a direct action on the secretory cell and indirectly by vasoconstriction and that both these effects are mediated through the alpha‐receptor.

Electrical stimulation of the central end of the vagal communicating branch in the thorax at frequencies between 2 and 20 Hz elicited, after a latency of 7.2 +/‐ 0.8 s, large‐amplitude colonic contractions. 5 Hz stimulation gave near maximal contractions and, because vomiting was more likely to occur at higher stimulus frequencies, was used as the standard stimulus for subsequent experiments. At this frequency the peak colonic contraction was 6.5 +/‐ 0.9 kPa. Following atropine the characteristics of the response to central vagal stimulation differed from that seen before atropinization. The latency was longer (45.7 +/‐ 8.2 s) and the amplitude greatly attenuated (0.7 +/‐ 0.2 kPa). Cooling the vagus nerves to 2 degrees C at a level either above or below the site of stimulation completely abolished both the cholinergic and the atropine‐resistant colonic responses to central vagal stimulation. These results are consistent with the vagus containing two motor pathways to the colon which are reflexly stimulated by a vagal afferent input. The functional significance of these reflexes is discussed.

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.

1. A technique is described for perfusing the isolated cat pancreas with saline solutions.

1. Adrenaline and noradrenaline cause a biphasic change in the transverse electrical conductance across the cat pancreas. After a latent period of from 5 to 30 sec a phase of decreased conductance lasting about 30 sec occurs which gives way to a phase of increased conductance lasting from 5 to 8 min.

1. In the isolated cat pancreas, stimulated maximally with secretin, increasing the perfusate potassium concentration (at the expense of sodium ions) caused a copious secretion of amylase from the gland, reduced the volume rate of secretion and caused vasoconstriction.

1. Amylase secretion from the perfused pancreas consists of two components: a small continuous basal secretion and a stimulated secretion in response to acetylcholine or cholecystokinin‐pancreozymin. The response to small doses of either stimulant was repeatable over several hours.

1. Electrical stimulation of the cut peripheral end of the splanchnic nerves results in a biphasic change in electrical conductance measured across the tail of the pancreas. A phase of decreased conductance is followed by a more prolonged phase of increased conductance.

1. The bicarbonate concentration in cat pancreatic juice falls and the chloride concentration increases at slow secretory rates. The concentration of sodium and potassium remain constant at all secretory rates.

1. The rate of secretion from a saline‐perfused preparation of the cat's pancreas is directly proportional to the perfusate bicarbonate concentration. When all bicarbonate is omitted, secretion completely or almost completely ceases.

1. Intra‐arterial injection or infusion of prostaglandins E1and E2into anaesthetized cats caused a fall in arterial blood pressure, a reduction in pancreatic blood flow and an inhibition of secretin‐stimulated pancreatic electrolyte secretion. In some experiments these effects were preceded by a transient increase in blood flow and secretion.

1. Following an I.V.injection of secretin into anaesthetized cats, the pancreatic cyclic AMP concentration rose within 30 sec and reached near‐maximal values within 1 min. Pancreatic secretion began only after 45 sec. As secretion declined, the cyclic AMP concentration also fell. However, after 40 min, when secretion had ceased, the concentration again rose, reaching a maximum after about 80 min and returned to basal values within 140 min.

1. The effects of dibutyryl cyclic adenosine 3′,5′‐monophosphate (dibutyryl cyclic AMP) and theophylline have been tested in the stimulated and unstimulated perfused cat pancreas.

1. [4-(14)C]Testosterone was administered intravenously to anaesthetized male cats as a single injection or as a 45-60min. infusion. 2. Most of the administered radioactivity was excreted in the bile (70-80%); only 2.9-5.5% of the dose was excreted in the urine. 3. Bile and urine samples were hydrolysed successively to yield glucuronide,;cold-acid-hydrolysed′ and; hot-acid-hydrolysed′ fractions. 4. The proportion of glucuronides in bile decreased in successive samples, but cold-and hot-acid-hydrolysed metabolites showed no consistent change. 5. After hydrolysis most of the radioactivity in both bile and urine could not be extracted by ether from neutral aqueous solution.

1. In fasted anaesthetized cats which were secreting pancreatic juice at a steady slow rate in response to continuous intravenous infusion of secretin, stimulation of the dorsal vagus trunk increased the rate of secretion, the rate of output of amylase and the concentration of bicarbonate in the juice.

1. The electrical properties of the resting and stimulated pancreas have been studied in the anaesthetized cat. There is an inverse relationship between the frequency of applied alternating current and the resistivity and dielectric constant of the resting pancreas. The resistivity is also affected by the fat content of the gland. The impedance locus of the pancreas is similar to that of other tissues.

1. Extracts of antral mucosa increase the output of pancreatic amylase. They do not stimulate the resting pancreas of the anaesthetized cat to secrete juice, but have a slight ‘secretin‐like’ effect on a pancreas already responding to endogenous or exogenous secretin.