Concentrations Of Pentagastrin Research Articles

Pepsin secretion by the totally isolated, vascularly perfused rat stomach.

The gastric pepsin output by the totally isolated, vagally denervated, and both luminally and vascularly perfused rat stomach was studied. Basal release of pepsin was 3% of total gastric mucosal stores per hour. Topical (luminal) administration of 0.001 M HCl was without effect. Graded concentrations of pentagastrin, gastrin, histamine, and impromidine in the vascular perfusate were tested. Pentagastrin induced only a slight increase in pepsin release (15% of total content per hour). Gastrin had a more pronounced effect and elicited a significant increase in the pepsin output, reaching a maximum of 28% of total pepsin content per hour. The CD50 of gastrin was 0.061 nM. Histamine and impromidine likewise produced significant increases in the pepsin secretion (maximum, 40% and 35% of total stores per hour, respectively). When the CD50 of histamine (0.718 microM) was compared with that of impromidine (0.011 microM), impromidine on molar basis had 65 times higher potency than histamine as a pepsin secretagogue. When the pepsin and acid responses during gastrin, histamine, and impromidine stimulation were compared, the pepsinogen secretion was shifted to the left and thus was more sensitive to stimulation than the acid secretion.

Calcium utilization by dispersed canine gastric smooth muscle cells

Smooth muscle cells were isolated by collagenase digestion from the circular layer of the canine gastric corpus, and cell length was measured by image-splitting micrometry. Cells contracted following incubation with KCl, carbachol, and pentagastrin. While contraction induced by 40 mM KCl was inhibited by adding nitrendipine (10 nM) or by removing extracellular calcium and adding EGTA (2 mM), the contraction induced by carbachol (10 pM) was not affected by these measures. Nitrendipine partially inhibited contraction induced by pentagastrin, and pentagastrin also contracted cells that had been depolarized by prior exposure to KCl and nitrendipine. Removing extracellular calcium and adding EGTA partially inhibited contraction induced by maximally (10 pM) or submaximally effective (0.3 pM) concentrations of pentagastrin but did not affect that induced by 300 pM pentagastrin. These results indicate that isolated smooth muscle cells utilize calcium for contraction by three distinct mechanisms. The extent to which each mechanism contributes to contraction depends on the nature of the stimulus and, in the case of pentagastrin, the concentration of the stimulating ligand.

The effect of pentagastrin on the gastric secretion by the totally isolated vascularly perfused rat stomach.

Gastric acid and pepsin secretion by the totally isolated vascularly perfused rat stomach was studied. Rat stomachs were vascularly perfused with Krebs-Ringer buffer gassed with 96% O2-4% CO2 and containing 5 mM glucose, 5 mM pyruvate, 4% bovine serum albumin, 10% ovine erythrocytes, and various concentrations of pentagastrin. The gastric lumen was perfused with distilled water gassed with 100% O2. To remove preformed juice and to enable preformed pepsin to be washed out, the initial 20-min gastric juice was discarded. The gastric effluent was then collected continuously for six 10-min periods, and the H+ concentration was determined by titration and the pepsin concentration estimated by a hemoglobin digestion method. Inclusion of pentagastrin in the perfusion buffer increased the acid output dose-dependently from 2.3 +/- 0.4 mueq/h during the control perfusion to a maximum of 12.7 +/- 2.1 mueq/h (p less than 0.01). With the higher doses of pentagastrin and concomitant high acid secretion, gastric acid secretion faded during the collection period. In contrast, gastric pepsin secretion was virtually unaffected by pentagastrin. The present model should be useful for studying the regulation of gastric acid and pepsin secretion.

Effect of Pentagastrin on Gastric Acid Secretion in the Totally Isolated Vascularly Perfused Rat Stomach Stimulated with the Phosphodiesterase Inhibitor Isobutyl Methylxanthine

The development of a very sensitive stomach biomodel, using the totally isolated rat stomach, is reported. Pentagastrin-stimulated acid secretion in anesthetized and conscious rats was also studied, and the capacity to produce acid and the sensitivity towards pentagastrin in the different rat stomach models were compared. The secretory capacity and the sensitivity were evaluated by means of the maximal acid output (MAO) and threshold dose (TD), respectively. Conscious rats provided with gastric fistulas had a MAO of 48 +/- 6.3 mu eq/10 min and a TD of 6 micrograms/kg-h. In anesthetized rats with luminally perfused stomach MAO was reduced to 11.6 +/- 1.2 mu eq/10 min, whereas the sensitivity was increased, as indicated by a TD of 0.5 micrograms/kg-h. Totally isolated vascularly perfused rat stomachs without isobutyl methylxanthine (IMX) produced even less acid (MAO, 2.2 +/- 0.4 mu eq/10 min) without any change in demand for stimulant (TD, 0.25 micrograms/stomach-h). Addition of IMX to the vascular perfusate in the isolated stomach preparation increased the MAO to 8.0 +/- 1.0 mu eq/10 min and induced a remarkable reduction in demand for stimulant, with a TD obtained already at a pentagastrin dose of 0.008 micrograms/stomach-h, corresponding to a concentration of pentagastrin in the vascular perfusate medium of 84.5 pM. Accordingly, the totally isolated vascularly perfused rat stomach stimulated with IMX is the most sensitive bioassay for (penta)gastrin so far reported.

Pentagastrin-stimulated gastric acid secretion by the isolated perfused rat stomach.

The purpose of this present study was to develop a method for stimulation of acid secretion by the isolated perfused rat stomach. Rat stomachs were perfused in situ via the abdominal aorta and celiac axis with Krebs-Ringer bicarbonate buffer in the presence or absence of 10% ovine erythrocytes. The gastric lumen was perfused with distilled water and gastric contents were collected at frequent intervals through a catheter at the pylorus. Sixty minute gastric acid output in response to various concentrations of pentagastrin was determined by titration of gastric contents with 0.01 N NaOH to pH 7.0. During arterial perfusion with Krebs-Ringer bicarbonate buffer in the absence of ovine erythrocytes gastric acid output was 2.50 +/- 0.58 SEM microEq H+/h, which did not increase in response to perfusion with Krebs-Ringer bicarbonate buffer containing pentagastrin. However, inclusion of 10% ovine erythrocytes in the arterial perfusate resulted in substantial stimulation of gastric acid by pentagastrin: maximal acid output, achieved with a pentagastrin dose of 0.6 microgram/kg/h, was 23.5 +/- 3.73 microEq H+/h (p less than 0.01). The results of the present study demonstrate the capacity of the isolated vascularly perfused rat stomach to secrete acid and provide a model for studying interactions of gastrointestinal regulatory peptides and their physiologic roles in the regulation of gastric acid secretion.

Acid secretion by isolated canine gastric mucosa.

1. An isolated gastric mucosal preparation from the dog stomach which is capable of acid secretion is described. Average values for normal resting potential difference (p.d.) was 49 +/- 2 mV (mucosal side negative with respect to the serosal side), short-circuit current (Isc) was 172 +/- 4 muA and resistance (R) was 285 +/- 6 omega.cm2. Low rates of spontaneous acid secretion (0-0.58 muequiv/cm2.hr) were present initially but following short-circuiting of the tissue these values decreased to low levels (less than 0.1 muequiv/cm2.hr) within an hour. 2. Histamine in doses exceeding 10(-6)M stimulated acid secretion, increased Isc and decreased R. Concentrations ranging from 10(-5) to 8 X 10(-4)M produced maximal secretion. The maximal secretory rate achieved was 4.24 +/- 0.35 muequiv/cm2.hr. 3. Pentagastrin (10(-8)M) and acetylcholine (10(-6)--10(-5)M) also stimulated acid secretion with a lower maximal secretion as compared to histamine stimulation. These concentrations of pentagastrin and acetylcholine did not alter histamine stimulated acid secretion. Higher concentrations of pentagastrin (10(-6)M) and acetylcholine (10(-4) M) reversibly inhibited acid secretion of histamine stimulated mucosa. 4. These results demonstrate that there are many similarities between in vitro and in vivo findings on the dog stomach, indicating the great potential of the in vitro dog gastric mucosa for studies on the mechanism of action and interaction of gastric secretagogues.