Secretin Preparations Research Articles

A Comprehensive Review of the Ethnobotanical Uses, Pharmacological, and Toxicological Profiles of Piper capense L.f. (Piperaceae)

Commonly known as wild pepper, Piper capense (P. capense) is a culinary herb mainly used as a secret in preparation of “Nkui” and “Nah poh” in Bayangam, West Cameroon. However, it also has many interesting pharmacological properties, which is why the people of sub-Saharan Africa so highly prize it for the treatment of multiple human pathologies. This study aimed to highlight the traditional uses, phytochemical composition, biological activities, and toxicological profile of the P. capense plant, to draw the attention of pharmaceutical companies to its enormous potential for the development of future phyto- or pharmaceutical products. Documentary research was meticulously carried out in the Web of Sciences, Scopus, Pubmed/Medline, and Google Scholar databases according to PRISMA 2020 guidelines. The results show that extracts and compounds isolated from Piper capense have interesting anticancer, antibacterial, antimalarial, hypoglycemic, anti-epileptic, and antidepressant activities. Methanolic extracts and essential oils from P. capense exhibit no harmful effects when directly applied to normal human hepatocytes, umbilical cord cells, intestinal cells, and keratinocyte cell lines. Additionally, methanolic extracts administered acutely or subchronically at low doses (≤250 mg/kg body weight) in Wistar rats also demonstrate no adverse effects. In conclusion, given its interesting activities, P. capense is a viable option for developing new antimalarial, anticancer, antibacterial, hypoglycemic, anti-epileptic, and antidepressant drugs. However, many avenues still need to be explored before translation into drugs.

A Study on the Efficient Contracts of Sale in response to the Origin Verification of FTA: Focus on the KOREU FTA and KORUS FTA

Purpose - The purpose of this study was to examine the cases of disputes between customs authorities and applied companies related to the origin verification and to derive implications and countermeasures that should be noted when concluding trade contracts for FTA-using companies. Design/Methodology/Approach - This study focused on the Korea-EU FTA and the Korea-U.S. FTA relative to reviewing dispute cases between importers and Korean customs authorities over the origin verification. Through this, we presented the factors and main points that should be considered when preparing the FTA-enabled trade contract in connection with the relevant provisions of the CISG. Findings - First, the contract shall state the obligation of exporters and business partners to comply with the country of origin regulations and to provide the country of origin verification data. Second, the duty of cooperation in follow-up investigation and data storage related to the origin verification shall be specified. Third, in the case of exclusion of preferential treatment due to origin verification, the claim for the right to indemnity and the subject to the imposition of the additional tax shall be specified. Fourth, it is necessary to specify that sensitive information in the course of the origin verification inspection shall be provided to the agent if the information of origin falls under the trade secret in preparation for disputes arising from the refusal of the exporter and producer to cooperate with the data. Fifth, upon receipt of a request for data related to the origin verification from the other country or its customs authorities, it shall immediately include a mandatory provision to inform the counterparty of the progress of the country of origin investigation and the relevant details. Research Implications - Trade companies should be cautious when concluding FTA trade contracts between trading parties by reflecting case-by-case reviews of the customs authorities’ origin verification.

Teaching the role of secretin in the regulation of gastric acid secretion using a classic paper by Johnson and Grossman

The regulation of gastric acid secretion has been the subject of investigation for over a century. Inhibition of gastrin-induced acid secretion by the intestine-derived hormone secretin provides a classic physiological example of negative feedback in the gastrointestinal tract. A classic paper by Leonard R. Johnson and Morton I. Grossman clearly shows the ability of secretin to negatively regulate gastric acid secretion, providing students with an example of this feedback loop. In addition, this article demonstrates the step forward in gastrointestinal endocrinology that occurred when pure preparations of secretin and other gastrointestinal hormones first became available. The comparison of the effects of exogenous, purified secretin to the physiological stimulus of acid in the duodenum is an important example of how newly available reagents allow scientists such as Johnson and Grossman to clarify the mechanisms behind previously established processes. One or more figures from this classic paper can be used to give students insight into the role of secretin in the regulation of the function of the gastrointestinal tract and will also give students a clear example of how the careful experimentation and clear interest in gastrointestinal physiology led Johnson and Grossman to advance the field.

Effect of continuous intravenous infusion of secretin preparation secrepan in patients with hemorrhage from chronic peptic ulcer and acute gastric mucosal lesion (AGML)

The purpose of the present study was to investigate the hemostatic effect of continuous intravenous infusion of secrepan (secretin preparation, Eisai Company Ltd. Tokyo) on gastroduodenal hemorrhage in patients with chronic peptic ulcer and AGML (acute gastric mucosal lesion). The patients consisted of 37 cases of bleeding ulcer (13 cases of chronic peptic ulcer and 24 cases of AGML). Secrepan was infused at a rate of 2 U/kg/hr for the first 3 days and 0.5 U/kg/hr for the next 4 days. The cumulative hemostatic rate in the chronic peptic ulcer group was 53.9% after 36 hours, and 76.9% after 48 hours of infusion, but no significant change in rate was observed thereafter. The cumulative hemostatic rate in the AGML group was 52.2% after 36 hours, and 95.7% after 72 hours of infusion. The hemostatic rate in chronic peptic ulcer and AGML cases with only slight or moderate bleeding was 100%, and no recurrent hemorrhaging was observed. The hemostatic rate in chronic peptic ulcer cases with severe bleeding was 62.5% and in AGML cases with severe bleeding was 93.3%, and 7 of 15 cases showed recurrent hemorrhage. Our findings indicated that continuous intravenous infusion of secrepan had more favorable effects on AGML cases, than on chronic peptic ulcer cases.

Secretin provocation test in the diagnosis of Zollinger-Ellison syndrome.

The secretin stimulation test has become the preferred provocative test in suspected cases of Zollinger-Ellison syndrome. A pure secretin preparation, a gastrin-specific radioimmunoassay, and an appropriate sampling sequence are important for the proper interpretation of this test. Gastric acid analysis is necessary in the assessment of hypergastrinemia to confirm acid hypersecretion and exclude achlorhydria. When properly performed and interpreted, the secretin provocation test offers a safe, expeditious, and reliable means of evaluating patients with hypergastrinemia.

Effect of continuous intravenous infusion of secretin preparation (secrepan) in patients with hemorrhage from chronic peptic ulcer and AGML.

This study was conducted to evaluate the hemostatic effect of continuous intravenous infusion of secrepan (secretin preparation, Eisai Company Ltd. Tokyo) on gastroduodenal hemorrhage in patients with chronic peptic ulcer and AGML (acute gastric mucosal lesion). The patients consisted of 37 cases of bleeding ulcer (13 cases of chronic peptic ulcer and 24 cases of AGML). Secrepan was infused at a rate of 2U/kg/hr for the first 3 days and 0.5U/kg/hr for the next 4 days. The cumulative hemostatic rate in the chronic peptic ulcer group was 53.9% after 36 hours, and 76.9% after 48 hours of infusion, but no significant change in rate was observed thereafter. The cumulative hemostatic rate in the AGML group was 52.2% after 36 hours, and 95.7% after 72 hours of infusion. The hemostatic rate in chronic peptic ulcer and AGML cases with only slight or moderate bleeding was 100%, and no recurrent hemorrhaging was observed. The hemostatic rate in chronic peptic ulcer cases with severe bleeding was 62.5% and in AGML cases with severe bleeding was 93.3%, and 7 of 15 cases showed recurrent hemorrhage. Our findings indicated that continuous intravenous infusion of secrepan had more favorable effects on AGML cases, than on chronic peptic ulcer cases.

Human secretin: Biologic effects and plasma kinetics in humans

The action of synthetic human secretin, which differs in two amino acid residues from porcine secretin, was compared with synthetic porcine secretin in 6 healthy volunteers. Pancreatic secretion was assessed by a marker perfusion technique and plasma secretin concentrations were assessed by a specific radioimmunoassay. Increasing doses of either human or porcine secretin produced increasing bicarbonate output (p < 0.01), whereas trypsin and lipase were not stimulated over basal. The highest doses of secretin induced a significant increase in pancreatic amylase secretion. The two secretin preparations were found to be equipotent with respect to pancreatic secretion and plasma kinetics. Significant increases of plasma secretin were observed after a steak meal in 15 volunteers (p < 0.001). When human secretin was infused at postprandial concentrations, significant increases in pancreatic bicarbonate output were observed (p < 0.05). We conclude (a) that the substitution of two amino acids in human secretin does not affect biologic activity and plasma metabolism of the compound; (b) secretin does not stimulate pancreatic enzyme secretion at physiologic concentrations; and (c) the stimulatory effects of secretin on pancreatic amylase remain to be elucidated. The study suggests that human secretin is a true hormone.

Effects of Dose, pH, and Osmolarity on Nasal Absorption of Secretin in Rats II: Histological Aspects of the Nasal Mucosa in Relation to the Absorption Variation Due to the Effects of pH and Osmolarity

Nasal absorption of secretin in rats was enhanced in an acid solution, and the maximum absorption was observed at a sodium chloride solution molarity of 0.462. In order to examine reasons for the variation of absorbability caused by the change of pH and osmolarity in secretin preparations, both a pretreatment study, in which the nasal mucosa was treated with placebo prior to the administration of a secretin preparation, and a histological study were conducted in rats. The nasal absorption of secretin was determined by measuring the increased secretion of pancreatic juice. Similar profiles of nasal absorption, both after intranasal administration of secretin preparations and as a result of pretreatment effects, were obtained in studies of the effects of pH and osmolarity. However, in the pH-effect study, the absorption with the use of active preparations was observed to be significantly larger than that with the pretreatment effect below a pH of 4.79, and significantly smaller than that with the pretreatment effect at a pH of 7 to 8. The results of histological studies revealed structural changes of the epithelial cells of the nasal mucosa at pH 2.94, and shrinkage of epithelial cells was observed at a sodium chloride solution molarity of 0.462.

A new round in the discussion on the action of secretin on pancreatic protein secretion: a further study on the effect of secretin on pancreatic secretion in dogs.

Whether or not secretin stimulates pancreatic protein secretion is a controversial question. In this investigation, dose-response studies with different secretin preparations were performed in dogs with two different types of pancreatic fistulae. Pure natural secretin (Karolinska Institute, Stockholm), synthetic secretin (Hoechst, Frankfurt), synthetic secretin (Hoechst, Frankfurt), synthetic D-Ala17-secretin (Roche, Basel), and natural secretin (Kabi, Munich) were tested in dogs equipped with a Thomas cannula for collection of pure pancreatic juice. The synthetic secretin was also tested in dogs with a modified Herrera fistula. Potency of the pure natural and the unmodified synthetic secretins was similar. Whereas protein output was significantly stimulated by these secretin preparations, protein concentrations fell to approximately 10 mg ml-1 with incremental doses of infused secretin. The high protein concentrations of 60 up to 120 mg ml-1 found in pure basal pancreatic secretion, suggest that pancreatic protein output may have been a "washout" phenomenon, and that the increasing protein output values were due to rising volume flow of pancreatic juice which is not completely protein-free. Impure secretin preparations and indirect collection techniques also lead to an elevation of pancreatic protein output.

Neurotensin-like immunoreactivity in some preparations of secretin and cholecystokinin.

Commercially available cholecystokinin (CCK) from the Boots Company, Nottingham and to a lesser degree CCK from the Gastrointestinal Hormone Research Unit of Karolinska Institute Stockholm and from Kabi Diagnostica, Studsvik, and also secretin from the Boots Company have been found to contain neurotensin-like immunoreactive contamination. As neurotensin is able to stimulate pancreatic secretion, this admixture may be of relevance when pancreatic function is tested.

Biological profile of a secretin preparation with prolongated activity

Biological profile of a secretin preparation with prolongated activity

Pepsinogen release from isolated gastric glands.

The in vitro release of pepsinogen was studied using a preparation of isolated gastric glands from rabbits. The pepsinogen content of the glands was estimated to be about 700 U/mg dry wt. Spontaneous release of pepsinogen was found to be less than 1% of the total per hour and relatively constant for at least 2 h. Pepsinogen release was stimulated in a dose-dependent manner by both carbachol and isoproterenol. The cholinergic and beta-adrenergic stimulation was selectively inhibited by atropine and propranolol, respectively. Removal of external calcium inhibited the responses to both isoproterenol (partially) and carbachol (completely). Several agents, including histamine, prostaglandin (E2), and synthetic secretin, were found not to stimulate pepsinogen release. However, a crude secretin preparation (Boots) was found to produce significant stimulation. Dibutyryl cAMP increased pepsinogen release in a dose-dependent manner. Isoproterenol was found to increase the cAMP content of gastric glands and to stimulate adenylyl cyclase activity in homogenates. The beta-adrenergic stimulation of adenylyl cyclase was found to be selective for a population of gastric cells that was relatively depleted of parietal cells and distinct from the histamine-stimulated adenylyl cyclase activity. The results indicate that pepsinogen secretion by the gastric chief cell is regulated, in part, by separate cholinergic and beta-adrenergic mechanisms and that both calcium and cAMP play a role in this regulation.

Comparative effects of synthetic and natural secretin on pancreatic secretion and on secretin, insulin, and glucagon levels in man

The effect of synthetic secretin (Roche) on exocrine pancreatic secretion and on secretin, insulin, and glucagon levels was determined and compared with that of pure natural porcine secretin (GIH, Karolinska Institutet, Stockholm) in 10 healthy volunteers. The two secretin preparations were found to be equipotent. Equipotency applies to pancreatic secretion and to secretin and insulin plasma levels, whereas the plasma levels of glucagon were not affected by either drug. It is concluded that this synthetic secretin preparation is suitable for clinical and research purposes.

The effect of secretin on the exocrine and endocrine pancreas. Part III. Exocrine and endocrine responses to synthetic secretin in the perfused isolated rat pancreas (author's transl)

The effects of synthetic secretin on the rate of flow of pancreatic juice, the rate of output of amylase, and the rate of release of immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) were simultaneously investigated in the isolated perfused rat pancrease. In this experimental system, factors other than the direct effect of hormonal stimulus on the pancreas, such as the autonomous nervous system or alteration of blood glucose concentrations, could be eliminated while simultaneously determining pancreatic exocrine and endocrine function.Pancreases from male Wistar rats, weighing 250 - 300 g and fed ad libitum, were isolated and perfused according to the technique of Kanno. The pancreas was perfused with a Krebs Ringer bicarbonate solution of 4.6% dextran-T 70, 0.25% bovine serum albumin and 50 mg/100 ml glucose, and gassed constantly with a 95% 02, 5% CO2 mixture to achieve pH 7.4. Perfusate was administered into the superior mesenteric and celiac artery via a non-recirculating open circuit. Flow rate was kept at about 2.0 ml/min with the aid of a micro-tubing pump. The total portal effluent was collected in chilled tubes at 60 sec intervals for the measurement of IRI and IRG concentrations.Synthetic secretin was applied by changing the medium reservoir. When the effect of secretin was studied, a 20-min basal period was followed by a 20-min stimulatory period and then a 20-min recovery period.To determine whether secretin might require high glucose levels for an insulinotropic action, an infusion of secretin at a concentration of 100 ng/ml was superimposed on 100 and 150 mg/100 ml glucose stimulation.For measurement of pancreatic exocrine secretions, a calibrated capillary tube was attached to the free end of the pancreatic cannula, which was inserted into the distal end of the common duct at a point shortly before its entrance into the duodenum and tied in place. The proximal end of the bile duct was ligated. Every 10 min the capillary tube was replaced and the flow rate of the pancreatic juice was measured. The sample of juice was diluted with a 6% bovine serum albumin solution, and amylase activity was determined by the chromogenic method with blue-dyed starch polymer. Amylase activity was expressed as Somogyi units/10 min.IRI was measured by polyethylene glycol radioimmunoassay. IRG was determined by radioimmunoassay with the talc absorption technique. Rat insulin and porcine glucagon were used as standards in IRI and IRG assays, respectively.No changes of IRI levels in the perfusate were obtained with concentrations of synthetic secretin ranging from 0.01 ng/ml to 2 μg/ml. Secretin had no influence on glucose-induced IRI release when superimposed on 100 or 150 mg/100 ml glucose stimulation. On the other hand, uniphasic IRG release was elicited by synthetic secretin in a dose-related fashion in the presence of 50 mg/100 ml glucose. However, secretin-induced IRG responses were completely abolished in the presence of 100 or 150 mg/100 ml glucose.Contrary to our observations, most of the previous experiments have shown the insulinotropic effect of secretin but have failed to demonstrate the glucagonotropic effect. Moreover, Santensanio et al. have revealed the suppressive effect of secretin on basal and alanine-stimulated IRG secretion in dogs. The reason for this discrepancy between their results and ours is not apparent. It seems that not only species differences but also the doses and the preparation of secretin used, and the levels of glucose concentration perfusing the pancreas have played a part in the contrasting results.A dose-response relationship was obtained between synthetic secretin and the peak rates of the flow and output of amylase. Maximal flow rate of the pancreatic juice and amylase output were induced with a dose of secretin at 1 μg/ml.

Effect of secretion on the exocrine and endocrine pancreas Part V: Pancreatic exocrine and endocrine responses to secretion in rats in vivo and in vitro (author's transl)

Secretin is an established stimulator of exocrine pancreatic function and has been reported by some to also stimulate insulin release both in vivo and in vitro. Contrary to these observations with natural porcine secretin, synthetic porcine secretin has been revealed to have no influence on insulin release but does stimulate glucagon release from the isolated perfused rat pancreas. Unphysiologically large doses of synthetic porcine secretin has also been confirmed in in vivo experiments to be capable of stimulating not only glucagon but also insulin secretion from the rat pancreas. Thus, the discrepancies between our previous results with synthetic porcine secretin and those obtained with natural porcine secretin may be due to the differences of the preparations of secretin or to the species differences of the experimental animals, or of the experimental system itself.The present investigation was undertaken to determine the effect of natural porcine secretin on exocrine and endocrine secretions from the rat pancreas in vivo and in vitro.Pancreases from Wistar male rats were isolated and perfused according to the technique of Kanno. A Krebs Ringer bicarbonate solution containing 4.6% dextran T-70, 0.25% bovine serum albumin and 50 mg/100 ml glucose was used as a perfusion medium. Commercially available secretin (Secrepan®; Eisai Co., Ltd., Tokyo, Japan : supplied as lyophilized powder containing 30% pure natural porcine secretin and stabilizer), an inactive placebo of secretin containing cystaine and alanine as stabilizers for natural secretin, and 100% pure natural porcine secretin without stabilizer were used as stimulants of pancreatic exocrine and endocrine secretions.Overnight-fasted Wistar strain rats were used in the in vivo experiments. The rats were anesthetized with sodium pentobarbital by subcutaneous injection. The body temperature was held at 37°C by a heating pad. One of the following solutions was administered into the jugular vein by a single rapid injection : 1 and 50 U/kg natural porcine secretin (Se-crepan®), and a comparable dose of the placebo of secretin. Blood samples were collected from the portal vein at -10, 0, 2.5, 5, 10, 30 and 60 min.Immunoreactive insulin (IRI) was measured by polyethylene glycol radioimmunoassay. Immunoreactive glucagon (IRG) was determined by radioimmunoassay by means of dextran coated charcoal using antiserum 30 K. Rat insulin and porcine glucagon were used as standards in the IRI and IRG assays, respectively.The lowest secretin concentration causing a significant increase in pancreatic flow rate and amylase output from the isolated perfused rat pancreas was 1 mU/ml. The maximal pancreatic flow rate and amylase output required a secretin concentration of 1 U/ml. Higher concentrations of secretin, however, resulted in lower responses of both pancreatic juice flow and amylase output. Commercial secretin at concentrations of 1 mU/ml to 2 U/ml in the presence of 50 mg/100 ml glucose did not cause an increase in the IRI concentration in the portal effluent above the basal value. Secretin at the concentration of inducing the maximal pancreatic exocrine secretion with 50 mg/100 ml glucose (1 U/ml) was infused for 10 min in the presence of 100 and 150 mg/100 ml glucose to determine whether a threshold level of glucose was required for the insulinotropic action of secretin. Commercial secretin at a concentration of 1 U/ml elicited a significant short-termed increase in the IRI response to 100 and 150 mg/100 ml glucose, while 1 U/ml pure natural porcine secretin with-out stabilizer had no effect on IRI secretion, even when perfused with 100 or 150 mg/100 ml glucose.

Preparation and characterization of biologically active iodo- and [ 3H]secretin

Synthetic secretin has been iodinated at the N-terminal histidine, leading to an almost 100% yield of mono- and diiodo-secretin (“lodo-secretin”). The catalytic exchange of iodine against tritium results in the preparation of secretin labeled with tritium mainly at the histidine residue (7 Ci/mmol). Iodo-secretin and [ 3H]secretin have the same potency in stimulating pancreatic adenylate cyclase as secretin, but the apparent affinity of [ 3H]secretin for this enzyme is twice as high as for iodo-secretin. [ 3H]Secretin binds rapidly to pancreatic plasma membranes. Adding excess unlabeled secretin reduces the tracer binding by about 70%.

The chronically reserpinized rat as a possible model for cystic fibrosis. VII. Alterations in the secretory response to cholecystokinin and to secretin from the pancreas in vivo.

Summary: The chronically reserpinized rat has been proposed as an animal model for cystic fibrosis on the basis of morphologic and secretory alterations in the submaxillary gland and of abnormalities in pulmonary secretions. In this investigation, the volume and composition of pancreatic juice from reserpine treated rats (0.5 mg/kg/day) have been compared to those of untreated controls after stimulation with purified cholecystokinin (0.1 μ/ kg body wt) and with crude and purified preparations of secretin (6μ/100 g body wt) infused iv for 30-min periods. The results demonstrate that the treated animals secreted a significantly lower volume of pancreatic juice after stimulation with these secretagogues. Flow rates were also significantly reduced after stimulation with cholecystokinin and crude secretin. Protein and amylase outputs in response to cholecystokinin were smaller than in control animals after unrestricted feedings, but greater after a 24-hr fast. Total bicarbonate output was also reduced after stimulation with either crude or purified secretin and the normal excretion patterns for bicarbonate and chloride were either absent or reversed in the secretin-stimulated pancreatic juice of the treated animals. Whole pancreas homogenates from the treated animals showed significant increases in Ca++ and protein content. These results indicate that chronic administration of reserpine alters the secretion of water, protein, and bicarbonate from the rat pancreas and that it affects several of the exocrine glands involved in cystic fibrosis. These findings lend support to the concept of an animal model for the human disease. Speculation: The chronic administration of reserpine to rats has been shown to induce alterations in salivary and pulmonary secretions which resemble those seen in patients with cystic fibrosis. The concept of an animal model has been proposed on the basis of these observations. The pancreas is another exocrine gland prominently involved in cystic fibrosis and if it can be demonstrated that reserpine administration also induces alterations in pancreatic secretion, the concept of the animal model would be strengthened considerably.

Synthesis of phenolic group containing analogues of porcine secretin and their immunological properties.

Syntheses by the conventional method are described of Nalpha-tyrosylsecretin, [Tyr1]secretin, and Nalpha-beta-(4-hydroxyphenyl)propionylsecretin. Secretin and [Tyr6]secretin were also prepared by the synthetic route identical with those employed for construction of the above analogues. Purification of secretin and the analogues was conducted by ion-exchange column chromatography on CM-Sephadex and gel filtration. Immunological reactivities of these analogues were examined in the radioimmunoassay system for secretin using two different antisera raised against synthetic secretin in rabbits. The tracers used in this study were [125I]-[Tyr1]secretin and [125I]-[Tyr6]secretin. The dose-response curves of Nalpha-tyrosylsecretin, [Tyr1]secretin, and Nalpha-beta-(4-hydroxphenyl)propionylsecretion were essentially superimposable upon those of natural and synthetic preparations of porcine secretin in the systems used, while [Tyr6]secretin showed discrepancy in the curve. In addition, biological activities of the synthetic polypeptides were compared with that of natural porcine secretin in term of exocrine pancreatic secretory response in anesthetized dogs.

Activation of liver guanylate cyclase by bile salts and contaminants in crude secretin and pancreozymin preparations

Crude preparations of secretin or pancreozymin increased and at higher concentrations decreased guanylate cyclase (GTP pyophosphate-lyase, EC 4.6.1.2) activity from soluble and particulate fractions of rat liver homogenates. Partially purified and synthetic secretin were without effect as was the biologically active octapeptide fragment of pancreozymin. The active contaminants in these preparations survived boiling, saponification, and treatment with phospholipase A, trypsin and neuraminidase C. The activity was extractable with chloroform/methanol and did not survive ashing. Eight bile salt contaminants in crude secretin were obtained with thin-layer chromatography. Two of the contaminating bile salts that increased liver particulate guanylate cyclase activity were identified as taurodeoxycholate and either glycochenodeoxycholate or glycodeoxycholate; taurocholate was inhibitory. The sodium salts of cholate, deoxycholate, chenodeoxycholate and their glycine- or taurineconjugated forms either increased or decreased particulate and soluble rat liver guanylate cyclase activity depending upon their concentration. Thus, the previously reported stimulatory and inhibitory effects of secretin and pancreozymin preparations on guanylate cyclase activity are probably attributable to their bile salt contaminants.

The effects of glucagon, secretin, pancreozymin and pentagastrin on the hepatic arterial vascular bed of the dog.

1 The sympathetically-innervated arterial vascular bed of the dog's liver was perfused from a femoral artery. Arterial blood flow and perfusion pressure were monitored continuously and the hepatic arterial vascular resistance (HAVR) calculated from these measurements. 2 Commercial preparations of secretin, pancroezymin, glucagon and pentagastrin were administered by intra-arterial (i.a.) injection and infusion. 3 Secretin and pancreozymin by injection caused dose-dependent hepatic arterial vasodilatation, and on a molar basis were both more potent than glucagon or pentagastrin. 4 Intra-arterial infusions of secretin and pancreozymin caused hepatic arterial vasodilatation at calculated blood concentrations close to those measured under physiological conditions by other investigators. The vasodilatation was of the same duration as that of the hormone infusions. 5 Pentagastrin by i.a. injection caused dose-dependent hepatic arterial vasodilatation; by i.a. infusion, vasodilatation occurred but there was marked 'escape' from the effects during the continued infusion. 6 As reported previously, glucagon by injection caused dose-dependent hepatic arterial vasodilatation of long duration; by infusion, glucagon caused vasodilatation that persisted after the cessation of the infusion. 7 Glucagon infused i.a. inhibited the vasoconstricter effects of i.a. noradrenaline, over the same range of infusions that caused hepatic arterial vasodilatation. 8 Secretin or pancreozymin did not antagonize the effects of noradrenaline on the hepatic arterial vascular bed at any doses used. 9 Pentagastrin did not antagonize the vasoconstrictor effect of noradrenaline whether hepatic arterial vasodilatation resulted from the pentagastrin infusion, or not. 10 These results are discussed with respect to the possible control of the hepatic arterial vascular bed by gastrointestinal hormones.