Volume Rate Of Secretion Research Articles

Absence of a relationship between arterial pH and pancreatic bicarbonate secretion in the isolated perfused cat pancreas.

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.

Effect of 16, 16-dimethyl PGE2 on resting and histamine-stimulated gastric mucosal blood flow.

Using [14C]aminopyrine clearance as a measure of mucosal blood flow, 16,16-dimethyl PGE2 was administered orally as a single bolus and its effects on resting and histamine-stimulated gastricmucosal blood flow assessed in conscious dogs with vagally denervated gastric pouches. No effect on resting mucosal flow was observed with any of the doses (ie, 2, 10, and 50 microgram/kg) of prostaglandin given. In histamine-stimulated experiments, intravenous infusion of histamine dihydrochloride (1 mg/hr) elicited a significant (P < 0.0005) increase from basal in gastric acid production, volume output, and gastric mucosal blood flow which remained unchanged for the duration of the study. Prostaglandin (50 microgram/kg) significantly decreased (P < 0.0005) these secretory responses and markedly inhibited (P < 0.005) mucosal blood flow without altering the ratio (R) of flow to the volume rate of secretion. The observation that R was unchanged suggests that this inhibitory action of 16,16-dimethyl PGE2 on gastric secretion and blood flow was mediated through direct effects on gastric parietal cells rather than any primary alteration in the gastric microcirculation. We conclude that 16,16-dimethyl PGE2 given orally has no effect on the resting gastric mucosal circulation and that any reduction in mucosal flow during histamine stimulation is secondary to its inhibitory effects on gastric acid secretion.

The effects of a prostaglandin endoperoxide analogue on canine gastric acid and mucus secretion

The effects of U-46619, a stable analogue of the prostaglandin endoperoxide PGH2, were studied on canine gastric acid secretion, gastric mucosal blood flow, and secretion of mucus into gastric juice and compared to those of PGE2. U-46619 was approximately four and three times as potent as PGE2 in inhibiting acid secretion and stimulating mucus secretion, respectively. When infused at a low dose, U-46619 inhibited acid secretion directly without causing a decrease in the ratio of mucosal blood flow to volume rate of secretion (R), this effect being similar to that observed for PGE2. However, unlike PGE2, U-46619 when administered in a higher dose caused a decline in R while decreasing acid secretion and mucosal blood flow, suggesting a primary restriction of blood flow. The antisecretory effects of arachidonic acid may be due in part to the endogenous formation of prostaglandin endoperoxides as opposed solely to prostaglandin formation. Considering the antisecretory and mucogenic actions of U-46619, nontoxic analogues of prostaglandin endoperoxides may be of value as antiulcer agents.

The kinetics of pancreatic amylase secretion and its relationship to volume flow and electrical conductance in the anaesthetized cat.

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.2. The output of amylase in response to each stimulus occurred in a constant volume of approximately 15 drops (0.5 ml.) regardless of the rate of background secretin stimulated flow of water and electrolyte.3. It is argued that because amylase secretion occurs in this constant volume, it is due to the rapid secretion of enzyme into the duct system from the acini, and subsequently the secretin stimulated secretion of water and bicarbonate washes the enzyme from the duct system.4. When enzyme secretion is stimulated an increase in the electrical conductance (measured at 1.592 kHz) occurs across the tail of the pancreas. This increased conductance has two components. An early peak associated with the extrusion of enzyme from the acinar cell and a later peak which is probably due to vasodilatation.5. Atropine was without effect on both enzyme secretion and the conductance record when the stimulant was CCK-PZ. Atropine blocked enzyme secretion and both peaks of the conductance record in response to stimulation by acetylcholine. Atropine blocked enzyme secretion and abolished the early phase of the conductance record, on vagal stimulation. It was without effect on the later peak which probably indicates an atropine resistant vasodilation of the pancreatic vessels.6. When the vagus is stimulated on a background of submaximal electrolyte secretion caused by the intravenous infusion of secretin, the volume rate of secretion and the rate of amylase secretion follow a similar time course. The maximal volume response occurred between 7 Hz and 15 Hz and the maximal amylase output per impulse was at 5 Hz.

The influence of the splanchnic nerves on the external secretion, blood flow and electrical conductance of the cat pancreas

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.2. Simultaneous measurements of pancreatic blood flow indicate that the phase of decreased conductance occurs as a result of vasoconstriction, whilst the phase of increased conductance is due to vasodilatation.3. The initial phase of decreased conductance and vasoconstriction is abolished by alpha-receptor blocking agents such as phenoxybenzamine and the phase of increased conductance blocked by beta-receptor blocking agents such as pronethalol.4. Short periods of electrical stimulation applied to the splanchnic nerves result in a secretion of amylase and a reduction in the volume rate of secretion.5. When the vasoconstrictor response was abolished by phenoxybenzamine, nerve stimulation still reduced the rate of secretion, suggesting that the inhibitory effect is in part due to a direct action of the secretory cells.6. After bretylium tosylate, splanchnic nerve stimulation no longer produced vasomotor changes in the pancreas and the inhibitory effect on the volume response was converted to one of augmentation, but the secretion of enzymes was unaffected.7. The secretion of amylase on splanchnic stimulation was abolished by intravenous injection of atropine, suggesting that a cholinergic mechanism is involved.8. Noradrenaline did not mobilize pancreatic enzymes.

The relation between the rate of production of gastric juice and its electrolyte concentrations.

1. Repeated 15-min collections of gastric juice were made during the plateau of response to an intravenous infusion of histamine diphosphate 0·01 mg h−1 kg−1 and the samples measured and their electrolyte concentrations estimated. A linear relationship was found between chloride output and the volume-rate of overall secretion and between hydrogen ion output and the same rate of secretion, while a multivariate linear relationship was also found between all three variables. 2. A mathematical analysis of these results suggests that if gastric secretion consists of an acid and a non-acid component, each of fixed composition, then the acid component has the composition H = 143 mEq/l, K = 16 mEq/l, Cl = 169 mEq/l, and the non-acid component is secreted at the same rate in different subjects under these circumstances. 3. The data enable gross sampling and analytical errors to be detected; in particular, the volume-rate of secretion can be predicted from hydrogen ion concentration, better from chloride ion concentration, and best from the concentrations of both ions. 4. For single samples such predictions appear to be superior to the direct measurement of volume.

Effect of Adrenalectomy and Glucocorticoids on the Secretion and Absorption of Hydrogen Ion

The effect of bilateral adrenalectomy on the secretion and absorption of acid in Heidenhain pouch dogs has been investigated. It was found that bilateral adrenalectomy significantly decreased the acid output to varying doses of histamine and did not alter the relation between hydrogen ion concentration and the volume rate of secretion. The absorption of acid by the gastric mucosa was not changed by adrenalectomy. Glucocorticoids but not mineralocorticoids restored secretion to normal levels. These experiments indicate that the impaired secretion of acid in response to histamine in adrenalectomized dogs is not attributable to increased leakage of secreted acid from lumen to blood.

Electrolyte composition of histamine stimulated gastric juice from intact stomachs of unanesthetized dogs.

SummaryAnalyses of gastric contents collected during a 3-hour infusion of histamine (maximal stimulation) in unanesthetized, gastric fistula dogs revealed statistically significant negative correlations between [Na+] and [H+], and between [K+] and [H+]. K+ output, H+ output, and Cl- output were positively correlated with output of water during this infusion. [K+] and volume-rate of secretion were inversely correlated during the first hour of infusion and positively correlated during the second and third hours.