Effect of natural peptide YY on blood flow and exocrine secretion of pancreas in dogs

Little is known regarding the mechanism by which peptide YY exerts an inhibitory effect on exocrine pancreatic secretion. The purpose of this study is to determine if peptide YY affects pancreatic blood flow with simultaneous measurement of exocrine pancreatic secretion in dogs. Pancreatic blood flow was measured by a laser Doppler flowmeter which allows continuous measurement of tissue blood flow. Natural peptide YY (0.1, 0.5, 1g/kg) was infused intravenously as a bolus under background infusion of secretin (1 unit/kg/hr) in combination with cholecystokinin-octapeptide (0.1g/kg/hr). Peptide YY caused a reduction of pancreatic blood flow in a dose-dependent manner as well as inhibition of pancreatic protein output, attaining the maximal reduction (28±4%) and inhibition (45±9%) at a dose of 1 g/kg, respectively. Simultaneous and continuous observation on tissue blood flow and exocrine secretion of the pancreas revealed that there was a highly significant correlation between the percent reduction of pancreatic blood flow and that of volume of pancreatic juice in response to peptide YY (r=0.849, P < 0.001). This study provides evidence that the mechanism of peptide YY-induced inhibition of exocrine pancreatic secretion is mediated, at least partly, through the decreased pancreatic blood flow.This study was supported by a grant from the Ministry of Education, Japan (A,61440060).A portion of this work was presented at the American Gastroenterological Association Meeting in New York in May 1985.     

Effect of somatostatin and thyrotropin-releasing hormone on cholecystokinin-induced gallbladder emptying

The effect of somatostatin (0.05 and 1.5 g/kg/hr) and of thyrotropin-releasing hormone (0.1 and 1.0 g/kg/hr) on cholecystokinin-induced gallbladder emptying was studied in healthy volunteers by means of real-time ultrasonography. In addition, the action of increasing doses (0.05, 0.15, 0.45, and 1.35 g/kg/hr) of somatostatin on resting gallbladder volume was also evaluated. Somatostatin, at the dose of 0.05 g/kg/hr (shown to produce blood levels similar to those measured after a meal) significantly inhibited the gallbladder contraction in response to cholecystokinin. Kinetic analysis showed that the interaction of somatostatin and cholecystokinin is of the noncompetitive type. The higher dose of the peptide (1.5 g/kg/hr) completely suppressed cholecystokinin-induced gallbladder contraction. In experiments carried out using somatostatin alone, a progressive increase in gallbladder volume in response to increasing doses of peptide was observed. The administration of either dose of thyrotropin-releasing hormone did not affect gallbladder emptying in any of the subjects studied. It is concluded that somatostatin is a potent inhibitor of cholecystokinin action on the gallbladder. The clear effectiveness of a very low, presumably physiological, dose indicates that somatostatin may play a physiological role in the regulation of gallbladder motor activity and provides further evidence that the peptide may act as a true hormone in man. Thyrotropin-releasing hormone does not seem to affect gallbladder motility, at least under the experimental conditions of the present study.     

Kinetics of atropine inhibition of pentagastrin-stimulated H+, electrolyte,and pepsin secretion in the dog

The effects of atropine on pentagastrin-stimulated gastric secretion of water, H, Cl, Na, K, and pepsin were determined by kinetic analysis of dose-response studies in 5 dogs with esophagostomy and gastric cannula. First a dose-response study was done using 7 doses of pentagastrin (1–6 g/kg hr), each dose given by I.V. infusion for 4 hr at a separate time. The same series of doses was used with atropine sulfate 10 g/kg hr as background. Atropine inhibited pentagastrin-stimulated secretion competitively with a dose ratio change of 20. In a third set of studies pentagastrin was infused alone for 4 hrs in the dose of 1.5 g/kg hr and then with each of 7 doses of atropine (0.625–40 g/kg hr), each dose used separately. Atropine competitively inhibited water, H, Cl, and K secretion, withK _i (dose of atropine giving 50% inhibition) of 1.0 g/kg hr. Pepsin secretion was much more strongly inhibited than acid secretion by atropine withK _i 0.27 g/kg hr and the inhibition was uncompetitive. Calculated maximal inhibition of H⁺ secretion by atropine was 89% and of pepsin 95%. Furthermore the shape of the response to pentagastrin was altered by atropine so that the peak response was delayed to the third and fourth hour of pentagastrin infusion.This study was supported by Public Health Service grants Nos. AM09260 and TIAM5286 from the National Institutes of Arthritis, Metabolism, and Digestive Diseases.     

Stimulated pancreatic exocrine secretion does not require pancreatic hyperemia in rats

Although blood flow and cholinergic tone influence gastric and salivary gland secretion, their role in pancreatic secretion is poorly defined. The purpose of the present study was: (1) to test the hypothesis that an increase in pancreatic blood flow accompanies stimulated pancreatic exocrine secretion, and (2) to examine the effects of cholinergic agents on basal and stimulated blood flow using hydrogen gas clearance. Stimulated pancreatic exocrine secretion (secretin 0.4, 0.8, ..6 g/kg/hr) resulted in a significant (P<0.005) increase in secretory volume; however, pancreatic blood flow was not significantly changed, and a negative correlation between blood flow and secretion was observed. A pharmacologic dose of secretin (5.0 g/kg/hr) resulted in a significant (P<0.05) increase in pancreatic blood flow, which was inhibited by atropine (5.0 g/kg/hr) infusion. Although 2-deoxyglucose caused a significant decrease (P<0.03) in basal pancreatic blood flow, atropine had no effect on basal blood flow levels. These observations suggest that: (1) under physiologic conditions, secretin- or 2-deoxyglucose-stimulated pancreatic secretion does not require pancreatic hyperemia; (2) a pharmacologic dose of secretin does produce pancreatic hyperemia, perhaps through a local cholinergic mechanism; (3) peripheral cholinergic tone does not contribute significantly to basal pancreatic blood flow; and (4) basal pancreatic blood flow may be influenced by central mechanisms.A portion of this work was presented at the annual meeting of the American Gastrointestinal Association, 1989, Washington, DC, and published in abstract from inGastroenterology 96:A97, 1989.     

Biphasic action of intravenous ethanol on dog exocrine pancreatic secretion

The effect of a 20-min intravenous infusion of 1 g/kg of ethanol on a 15% (w/w) solution in isotonic saline on pancreatic secretion was determined in six conscious Beagle dogs provided with Thomas cannulae. Ethanol was given on a background of a prolonged infusion of 0.5 CU/kg/hr of secretin alone or secretin plus either different doses of cerulein (12.5–200 ng/kg/hr), 3 μg/kg/hr of pentagastrin, or 200 μg/kg/hr bethanechol. Intravenous ethanol had a biphasic action on pancreatic secretion: inhibition during the first 40 min followed by stimulation. When compared to control experiments with intravenous infusion of saline, the inhibition was statistically significant only for volume and bicarbonate output against a background of pentagastrin and for protein output against a background of bethanechol. We propose that alcohol inhibits acetylcholine-mediated protein secretion. We delayed stimulatory effect of ethanol was statistically significant for both ecobolic (protein output) and hydralatic (water and bicarbonate) secretion during infusion of secretin plus 12.5–25 ng/kg/hr cerulein, but not with doses of 50 ng/kg/hr. Although the plateau of secretion before alcohol was roughly similar in the experiments using cerulein and bethanechol, ethanol inhibited protein output and had no effect on bicarbonate output during stimulation with bethanechol Therefore, the effects of alcohol on pancreatic secretion are influenced by both the type of stimulation and its intensity (dosage).     

Comparison of gastric inhibitory polypeptide and intraduodenal or intravenous fat on gastric acid secretion from vagally innervated and denervated canine stomach

Gastric inhibitory polypeptide (GIP), given to dogs in graded doses (range 0.25–2 g/kg/hr) against a constant background stimulation with pentagastrin (4 g/kg/hr), failed to affect the acid secretion at all doses used except the largest one (2 g/kg/hr) which significantly reduced the acid secretion only from the vagally denervated portion of the stomach (Heidenhain pouch, HP) while raising plasma GIP two to three times above the levels reached with duodenal fat. GIP infused in a constant dose (1 g/kg/hr) significantly reduced the HP responses to lower (0.5–2 g/kg/hr) but not to higher (4–16 g/kg/hr) doses of pentagastrin, the kinetics of this inhibition being of competitive type. GIP was ineffective against a constant near maximal stimulation with pentagastrin (4 g/kg/hr), histamine (40 g/kg/hr), or liver extract meal, whereas fat (10 g), given intraduodenally or intravenously, was a powerful inhibitor of acid responses to these stimulants both from the innervated and denervated stomach. Plasma GIP reached similar levels with exogenous GIP and duodenal fat but remained unchanged with intravenous infusion of fat.     

Effect of 15(R), 15-methyl prostaglandin E2 and indomethacin on pancreatic secretion in man

In addition to gastric mucosal cytoprotective and antisecretory effects, prostaglandin E₂ has a beneficial effect on experimental pancreatitis in some animal models, while prostaglandin synthesis inhibitors such as indomethacin and salicylates may induce pancreatitis at maximal doses. However, their effect on human pancreas is unclear. For this reason we considered it necessary to delineate their actions on human pancreatic secretion. Six healthy volunteers were studied on six separate days. On day 1, against a background of 1 pmol/kg/hr secretin, increasing doses of CCK were infused intravenously. On day 2, increasing doses of an amino acid mixture were infused intraduodenally and both studies were repeated on two occasions, following 100 g 15(R), 15-methyl prostaglandin E₂ per os on one and following indomethacin 50 mg orally 12 and 1 hr prior to the study on the other. Both indomethacin and PGE₂ had no significant effect on pancreatic secretion in response to graded doses of CCK. 15(R), 15-Methyl prostaglandin E₂ and indomethacin caused a reduction of amylase output in response to the higher doses of intraduodenal amino acids. The prostaglandin E₂ derivative also elicited a significant increase in basal bicarbonate output. In conclusion: the acute effects of 15(R), 15-methyl prostaglandin E₂ and indomethacin on human pancreatic secretion do not seem to offer an explanation for the mechanisms of protection against experimental acute pancreatitis or an association with pancreatitis, respectively.     

A new benzothiadiazine derivative,LN 5330: effects on pancreatic hormones

Summary LN 5330 is a new benzothiadiazine which is a structural analogue of diazoxide. Its effects in vivo were studied on blood glucose levels and insulin, glucagon and somatostatin secretion in normal dogs, and in vitro on glucagon and insulin secretion from the isolated perfused rat pancreas. The results were compared with those obtained with diazoxide at equimolar dose or concentration. In the normal anaesthetized dog having a T-shaped catheter inserted in the pancreaticoduodenal vein, the infusion of LN 5330 (87.8 mol/kg for 20 min) induced (1) a progressive increase in blood glucose levels, (2) a rapid decrease in insulin and somatostatin output rate, (3) an immediate increase in pancreatic glucagon secretion, and (4) a delayed decrease of arterial blood pressure. The equimolar dose of diazoxide provoked the same effects on blood glucose levels, insulin and somatostatin output, but a marked decrease in glucagon output and in arterial blood pressure. In the isolated rat pancreas perfused with 8.3 mmol/l glucose, the infusion of LN 5330 (440 mol/l for 30 min) induced a drastic fall in insulin and a rapid and persistent increase in glucagon output. This stimulatory effect on glucagon secretion was not found with diazoxide at equimolar concentration. These findings show that LN 5330 is a substance which is distinct from diazoxide and interesting because of its double action: inhibition of insulin secretion and stimulation of glucagon secretion.     

Effect of synthetic porcine neuropeptide Y (NPY) on splanchnic blood flows and Exocrine pancreatic secretion in dogs

This study examined the effect of synthetic porcine neuropeptide Y on the splanchnic blood flows and the exocrine pancreatic secretion in dogs. Graded doses of neuropeptide Y (0.1–5 g/kg, intravenous) caused dose-dependent reduction of the secretin-stimulated exocrine pancreatic secretion and of the blood flows in the superior mesenteric artery, the portal vein, and the pancreatic tissue. Neuropeptide Y at 5 g/kg reduced the blood flows to 45.9±13.3% (superior mesenteric artery), 63.0±10.5% (portal vein), and 77.9±4.8% (pancreatic tissue), respectively. This dose also reduced secretin-stimulated pancreatic juice volume and CCK-8 plus secretin-stimulated protein output to 65.2±9.3 and 63.3±14.0%, respectively. This study shows a potent vasoconstrictor effect of neuropeptide Y on splanchnic vessels. Neuropeptide Y also inhibited exocrine pancreatic secretion in a significant correlation with the reduction in pancreatic tissue blood flow, which suggests that reduction in the blood flow may be one of the possible mechanisms of the inhibitory action of neuropeptide Y on exocrine secretion.This work was supported by a grant from the Ministry of Education, Japan (A-61440060).     

Effect of gastric inhibitory polypeptide on pentagastrin-stimulated acid secretion in man

Eight male subjects were given pentagastrin by intravenous infusion in doses of 25, 74, 222, 667, and 2000 ng/kg/hr, each dose for 30 min. On another day the same subjects were given the same doses of pentagastrin while gastric inhibitory polypeptide (GIP) was being infused intravenously in a dose of 2 g/kg/hr. At the 222 ng/kg/hr dose of pentagastrin, acid output was significantly lower with GIP; at all other doses of pentagastrin, acid output did not differ significantly in tests with and without GIP. Pepsin output in the tests with and without GIP did not differ significantly at any dose of pentagastrin. Plasma concentration of GIP, measured by radioimmunoassay, showed a mean±SE plateau level of 7.4±1.4 ng/ml during GIP infusion and 0.4±0.1 ng/ml peak level after a standard meal. We conclude that the increase in blood concentration of GIP produced by feeding is probably inadequate to cause significant inhibition of gastric acid or pepsin secretion in man.     

Cerulein-induced acute pancreatitis in the rat

A study was made with different doses of cerulein (2, 4, 10 and 20 g/kg) administered subcutaneously to rats by four injections at intervals of 1 hr; the aim of this work was to study exocrine pancreatic secretion of the rat under cerulein-induced acute pancreatitis, analyzing enzyme and hydroelectrolyte secretion of pancreatic juice. A further aim was to study the relationship between the dose of cerulein and the plasma levels of peptides controlling hydroelectrolyte secretion of the pancreas, like secretin and vasoactive intestinal peptide (VIP). At the lowest dose schedule, the amounts of total protein and enzymes (amylase and trypsin) in pancreatic juice decreased significantly, plasma amylase increased, and the pancreas became edematous. Higher doses magnified these effects. By contrast, ductular function (flow and HCO ₃ ^– ) was well preserved in ceruleintreated rats, and this was probably due to the significant increase in plasma levels of immunoreactive secretin whereas VIP levels were unchanged. The secretin released by treatment with cerulein is able to palliate the lack of flow from acinar origin that is affected in the process of acute pancreatitis, being a beneficial response to the cerulein treatment.     

Effect of small doses of somatostatin analog,octreotide, on gallbladder contractility in normal Chinese adults

The acute effects of single different doses of the somatostatin analog octreotide on the contractility of the gallbladder stimulated by fatty meal were studied in six healthy Chinese volunteers. Gallbladder contraction after a fatty meal was significantly suppressed by octreotide at doses of 50, 25, 12.5, and 5 g. Mean duration of suppression lasted for more than 10 hr at doses of 25 and 50 g, after which the gallbladder contractility was restored at 24 hr in three and four, respectively, of the six subjects. The percentage of relative gallbladder contraction (PRGC) in all subjects receiving 12.5 and 5 g octreotide returned to pretreatment values at 10 hr but had not returned to normal 6 hr after the injection of 5 g octreotide. In summary, octreotide inhibits the contraction of the gallbladder even with a dose as low as 5 g. It appears that it may not be possible to avoid gallbladder dysfunction during long-term octreotide therapy by decreasing the dose. Further studies including modalities to increase the contractility of the gallbladder are recommended.     

Effect of somatostatin on diarrhea and on small intestinal water and electrolyte transport in a patient with pancreatic cholera

Summary The effects of somatostatin on diarrhea and on small intestinal flow of water and electrolytes (slow-maker perfusion technique) in a patient with pancreatic cholera are reported. Continuous intravenous infusion of somatostatin (8 g/kg/hr) suppressed the diarrhea, but a rebound was observed after somatostatin. Infusion of somatostatin at the same dosage decreased the ileal fluid flow rate to within control values. This effect was mainly due to a sharp reduction in the rate fluid entered the jejunum, but was also due to a suppression of the abnormal water and electrolyte secretion in the proximal jejunum. Secretion in the rest of the small bowel remained unchanged. Somatostatin did not noticeably after the high preinfusion plasma level of prostaglandin E₁, but decreased the initially high plasma concentration of vasoactive intestinal peptide to normal values. These results suggest that long-acting somatostatin analogs could be of value in the symptomatic treatment of diarrhea in pancreatic cholera.Supported by INSERM C.R.L. 79.5.453.7 to J.A.C.A part of this work has appeared as a letter in theLancet (2:476, 1979).     

Terbutaline,A β2-Adrenoreceptor agonist,inhibits gastric acid secretion and stimulates release of peptide YY and gastric inhibitory polypeptide in dogs

Terbutaline, a ₂-adrenoreceptor agonist, inhibits pentagastrin-stimulated gastric acid secretion. The purpose of this study was to examine the effect of intravenous administration of terbutaline on plasma levels of peptide YY(PYY) and gastric inhibitory polypeptide (GIP), both of which are known to inhibit gastric acid secretion. Seven dogs with gastric and duodenal fistulas were given pentagastrin (1 g/kg/hr) intravenously for 150 min in combination with terbutaline (10 or 20 g/kg/hr) or saline during the 60- to 120-min period of pentagastrin infusion. Pentagastrin-stimulated gastric acid secretion was significantly (P <0.05) inhibited by intravenous administration of terbutaline. Terbutaline significantly increased plasma PYY levels, 24% in response to terbutaline at 10 g/kg/hr, and 59% at 20 g/kg/hr. Plasma GIP levels were also increased significantly, 24% with terbutaline at 10 g/kg/hr, and 39% at 20 g/kg/hr. Our data suggest that terbutaline-induced inhibition of pentagastrin-stimulated gastric acid secretion is mediated, at least in part, by the release of PYY and GIP. The adrenergic nervous system may influence gastric acid secretion through the release of PYY and GIP.Supported by grants from the National Institutes of Health (5 R37 DK 15241-17, PO1 DK 35608, and RO1 DK 37406), and the John Sealy Memorial Endowment Fund (2723).     

Secretory component and lactoferrin in pure pancreatic juice in chronic pancreatitis

To evaluate pathophysiological roles of proteins in pancreatic secretion, immunoreactive lactoferrin (LF) and secretory component (SC) were measured in the first fraction of the pure pancreatic juice obtained endoscopically from 17 control, 21 suspected (SCP), 14 noncalcified (NCP), and 14 calcified chronic pancreatitis (CCP) subjects. The protein and amylase tended to decrease both in concentration and output from control to CCP. LF concentration was elevated in CCP (18.0±4.9/ml) when compared with controls (2.3±0.2g/ml), and LF output in NCP (12.3±3.8 g/min) was increased from controls (3.8±0.6 g/min). The combination of high LF concentration with low protein output was observed in 10/14 in CCP but 0/14 in NCP and can be a biochemical discriminator of CCP from NCP. SC concentrations were also elevated in NCP (8.5±2.0 g/ml) and CCP (5.6±1.6 g/ml) from controls (1.2±0.2 g/ml). SC outputs in SCP (9.8±3.1 g/min) and NCP (21.1±4.8 g/min) were increased from controls (1.7±0.3 g/min), but there was no further increase in CCP. Hypersecretion of LF and SC in chronic pancreatitis is different, especially in CCP, although the mechanisms for hypersecretion are unknown.This study was supported in part by a research grant for intractable pancreatic disease from the Ministry of Health and Welfare, Japan.     

Erythromycin stimulates gallbladder emptying and motilin release by atropine-sensitive pathways

The effect of administering different doses of erythromycin on gallbladder emptying and plasma concentrations of immunoreactive motilin was investigated in healthy volunteers. Erythromycin was infused for 30 min at four different doses: 20, 50, 100, and 1000 mg/hr. Gallbladder volume was determined by ultrasound scanning every 10 min for 60 min. All doses, except 20 mg/hr, provoked a significant reduction in gallbladder volume (P<0.01). The gallbladder emptying peak occurred after 20 min infusion. It was approximately 40–45% of basal volume and 60–70% of the emptying observed after a standard meal. At 100 mg/hr, erythromycin caused a 2.5-fold increase in plasma motilin concentration, which reached a peak after 30 min infusion. Plasma motilin peaked following maximum gallbladder emptying in all subjects. To evaluate whether cholinergic pathways were implicated in the action of erythromycin, 100 mg/hr erythromycin was infused together with 6 g/kg/hr atropine. Atropine inhibited both gallbladder emptying and motilin release (P<0.001). Infusion of 1 g/kg/hr somatostatin had the same inhibitory effects (P<0.001). Our results suggest that atropine acts by inhibiting an erythromycin-activated cholinergic neural mechanism. Somatostatin could exert its inhibitory effect by blocking the release of acetylcholine from neural terminations.     

Pancreatic Fluid Hypersecretion in Rats After Acute Pancreatitis

Pancreatic exocrine function was examined inrats during the early stage of acute pancreatitisinduced by four subcutaneous injections of 20 mug/kgbody weight of cerulein at hourly intervals. Basalpancreatic fluid secretion at 6 hr after the first of fourcerulein injections was significantly elevated (27.6± 3.7 vs 17.4 ± 2.1 l/30 min incontrol, P < 0.01) and further increased with time,reaching the peak level at 24 hr (105.1 ± 4.6 l/30 min).Intravenous infusion of loxiglumide (50 mg/kg bodywt/hr), atropine (100 g/kg body wt/hr), oranti-secretin serum did not modify the fluidhypersecretion observed at 24 hr after induction of acute pancreatitis.Loxiglumide, when given 30 min before the first ceruleininjection, markedly reduced fluid secretion, but couldnot inhibit the fluid hypersecretion when applied after the last cerulein injection. Leakage ofEvans blue dye into pancreatic juice was slightly butsignificantly increased in postpancreatitic ratscompared with that in the control rats (1.30 ±0.17 vs 0.75 ± 0.08 g/ml, P 0.01),whereas that in the pancreas was not different from thecontrol rats. In vivo labeling with5-bromo-2-deoxyuridine showed active proliferation ofacinar and ductular cells at 6 hr. In addition, the fluid was rich inchloride (137.1 ± 2.5 at 24 hr vs 92.4 ±3.3 meq/liter in control, P < 0.01) but poor inbicarbonate concentration (39.0 ± 2.0 at 24 hr vs46.5 ± 1.9 mmol/liter in control, P < 0.01), indicating acinar cell secretion.These results indicate that pancreatic fluid secretionduring the early stage of acute pancreatitis induced bysupramaximal doses of cerulein was markedly increased not by CCK-, secretin-, orcholinergic-dependent mechanisms but probably by acinarcell proliferation.     

Effect of intravenous infusion of somatostatin on gastric, pancreatic and biliary secretion in the rat.

The effect of somatostatin (GH-RIH) on gastric, pancreatic and biliary secretion was examined in the anesthetized rats. Intravenous infusion of the hormone, in graded doses ranging from 1 to 16 microgram/kg/hr, produced a dose dependent inhibition of pentagastrin, 1.5 microgram/kg/hr, induced acid secretion, reaching about 54% of control level at the dose of 16 microgram/kg/hr. Somatostatin, 4, 16 and 64 microgram/kg/hr, inhibited the pancreatic juice volume stimulated by intravenous injection of secretin, 1 u/kg, as a bolus. Somatostastin, 2, 8, 32 and 128 microgram/kg/30 min, did not change the bile flow rate in control period. Somatostatin may play a physiological role in the regulation of the secretory process of the stomach and pancreas.     

Dose–Effect Relationship of BB-10010/MIP-1 Alpha on Proliferation in Murine Small Intestinal Epithelium:

BB10010/MIP-1 alpha reduces the number of proliferating cells in the small intestine, strongly suggesting a radioprotective potential in this organ. This study was designed to optimize BB10010 administration for maximal radioprotection. In single administration protocols 1 or 4 mg/kg of BB10010 was injected into mice 2, 4 or 10 hr before death. In double administration protocols an initial dose of either 0.4 or 200 g/kg, and a second dose (2.5 hr apart) of 200 g/kg 4 hr before death were administered. The number of vincristine-arrested metaphases were counted on individually microdissected crypts from the midpoint of the small intestine. When compared to the smaller doses of BB 10010 used in our previous studies, the higher doses used in these experiments did not result in any further reduction in the number of proliferating cells under any of the protocols assessed. Furthermore, some values were found to be above not only those observed with the smaller doses, but also above untreated controls. It is concluded that a single dose of 200 g/kg of BB10010 offers the most consistent reduction of mitotic cells, and is, therefore, considered optimal for assessment of radioprotection.     

Effect of nicotine on serum secretin and exocrine pancreatic secretion

The effect of nicotine (100 g/kg hr^–1) on serum secretin and pancreatic secretions was studied in dogs with chronic pancreatic fistulas. Release of immunoreactive secretin (IRS) was stimulated by intraduodenal infusion of HCl (9.6 mEq/30 min). Pancreatic flow rate and bicarbonate and protein secretions were stimulated either by intestinal acidification or infusion of exogenous secretin (1.0 IU/kg hr^–1). It was found that nicotine delayed the appearance of peak IRS concentrations in response to intraduodenal HCl by about 20 min. However, nicotine had no effect on the total amount of IRS released nor was this delay accompanied by a similar delay in the appearance of peak bicarbonate output. Furthermore, nicotine did not affect pancreatic secretory function stimulated by either HCl or exogenous secretin. These data do not support the thesis that nicotine plays an important role in the pathogenesis of duodenal ulcers in smokers by inhibiting the pancreatic secretion of bicarbonate.