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Biomedical subjects

T E Adrian

Publications and source records attributed to T E Adrian.

At least 163 records · Page 9Linked to original sources
PubMed1989

Dopamine and neurotensin storage in colocalized and noncolocalized neuronal populations.

The effects of reserpine on dopamine (DA) and neurotensin (NT) levels were studied in four different brain regions of the rat. Reserpine (0.5-5.0 mg/kg i.p., 6, 18, 48 and 72 hr) produced a dose- and time-dependent decrease in both DA and NT levels in the prefrontal cortex, a brain region innervated by a mixed DA/NT projection. The effect of reserpine was not mimicked by alpha-methylparatyrosine (200 mg/kg i.p.) pretreatment. Furthermore, the reserpine-induced decline in prefrontal cortex DA and NT levels occurred after gamma-butyrolactone (GBL)-induced inhibition of impulse flow (750 mg/kg i.p.). In contrast, in the nucleus accumbens and striatum, regions which contain colocalized (nucleus accumbens) and intrinsic (striatum and nucleus accumbens) neurotensin perikarya, reserpine produced declines in DA and increases in NT levels. alpha-Methylparatyrosine decreased striatal and nucleus accumbens DA levels without altering NT levels in these structures. GBL produced an increase in DA levels in the nucleus accumbens and striatum while decreasing nucleus accumbens and striatal NT levels. Reserpine attenuated the decline in nucleus accumbens and striatal NT levels produced by GBL. In the periaqueductal grey, a brain region densely innervated by NT which has a small population of DA perikarya, reserpine had no effect on NT levels. Because there is no known colocalization of DA and NT in the striatum, the increases in striatal NT levels after depletion of DA may indicate that striatal DA afferents control the release and/or synthesis of NT within NT cells in the striatum, thus leading to alterations in striatal tissue levels.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Butyrolactone↗
PubMed1988

Peptide YY in diabetics treated chronically with an intestinal glucosidase inhibitor.

Peptide YY (PYY) is a recently discovered peptide found in the distal ileum and colon. It circulates in plasma and concentrations rise in malabsorptive conditions. The potential of PYY as an indicator of impaired carbohydrate digestion was studied in a pharmacological model of intestinal glucosidase inhibition. Thirteen type-2 diabetics on long-term treatment with the alpha-glucosidase inhibitor acarbose (3 x 100 mg per day) had test meals with and without acarbose 100 mg before and after the treatment period (mean 46 weeks), a test meal with acarbose after 20 weeks of continuous treatment and a final test meal without acarbose 6 weeks after cessation of treatment. Without acarbose mean plasma PYY concentrations rose from a mean basal value of 11.5 +/- 2.9 pmol/l to 19.5 +/- 3.9 pmol/l 120 min postprandially (P less than 0.01). Acarbose treatment did not effect basal plasma PYY concentrations but significantly enhanced food stimulated PYY concentrations acutely, at 20 weeks and at the final treatment test meal. Mean incremental integrated plasma responses (area under curve) rose by 183%, 184% and 169%, respectively (P less than 0.05). After cessation of treatment postprandial responses returned to pretreatment values within 6 weeks. Conversely, the integrated incremetal postprandial plasma responses of glucose and insulin were reversibly reduced by acarbose to 58% +/- 9% and 60% +/- 10% of controls, respectively. Self-assesed side effects of flatulence and more frequent bowel action showed no regular relationship to the PYY response. PYY seems to act as an indicator of the increased carbohydrate load to the distal intestine even in the absence of clinical symptoms. It may contribute to the hypoglycaemic effect of alpha-glucosidase inhibitors by slowing down intestinal transit.

Acarbose↗
PubMed1988

Identification and characterization of a cytosolic 30 kDa histamine stimulated phosphoprotein in parietal cell cytosol.

Histamine stimulated acid secretion is mediated by an increase in intracellular cAMP. Cytosolic protein phosphorylation stimulated by histamine was investigated in isolated rabbit parietal cells. Histamine stimulated the phosphorylation of a 30 kDa phosphoprotein with an isoelectric point of 5.6. Cimetidine completely inhibited histamine-stimulated pp30 phosphorylation. However, omeprazole had no effect on the phosphorylation of pp30. Forskolin and 8-bromo-cAMP also stimulated the phosphorylation of pp30. The results suggest that pp30 is a histamine-stimulated, cAMP-dependently phosphorylated protein substrate in parietal cell cytosol.

Animals↗
PubMed1988

Pepsin release by prostaglandin E1 analogue. A potential therapeutic problem.

Prostaglandins Inhibit gastric acid secretion and are independently "cytoprotective" for gastric mucosa. They are currently under clinical Investigation for the treatment of peptic ulcers. The effects of the prostaglandin E1 analogue misoprostol on pepsinogen and acid secretion were tested in isolated rabbit gastric glands and enriched parietal cells. Pepsinogen concentrations were measured by iodine 125-labeled albumin digestion and acid secretion indirectly by carbon 14-tagged aminopyrine uptake. Misoprostol inhibited histamine-stimulated acid secretion in parietal cells with 50% inhibition at 10(-9) mol/L and maximally (78% inhibition) at 10(-7) mol/L. In contrast, however, misoprostol strongly stimulated pepsinogen secretion by gastric glands with a half-maximal effect at 10(-8) mol/L and maximal stimulation of 227% at 10(-6) mol/L. It is possible that this release of pepsin could compromise the action of prostaglandins in promoting ulcer healing.

Alprostadil↗
PubMed1988

Dissociation of pepsinogen and acid secretion in the guinea pig.

In vivo observations have suggested that acid secretion may potentiate pepsinogen release. We measured pepsinogen and acid secretion by guinea pig fundic mucosal sheets stimulated by 10(-4) M histamine, 10(-8) and 10(-9) M cholecystokinin, and 3 x 10(-7) M carbamylcholine and then investigated the effects of 10(-4) M omeprazole on basal, carbachol-stimulated, and cholecystokinin-stimulated secretion. Histamine increased basal acid secretion fivefold (p less than 0.01) without altering pepsinogen secretion. Cholecystokinin did not stimulate acid secretion but increased pepsinogen secretion by factors of 23.1 at 10(-8) M and 9.1 at 10(-9) M (both p less than 0.01). The combination of 10(-4) M histamine and 10(-9) M cholecystokinin increased acid secretion 3.5-fold and pepsinogen secretion 6.4-fold, statistically equivalent to the sum of the effects of histamine and cholecystokinin alone. Carbachol increased acid secretion and pepsinogen secretion by factors of 4.0 and 10.9, respectively (both p less than 0.01). Pretreatment with 10(-4) M omeprazole abolished basal and carbachol-stimulated acid secretion. However, pepsinogen secretion was unaffected (p greater than 0.05). Furthermore, omeprazole-treated tissues increased pepsinogen secretion by factors of 10.0 with 3 x 10(-7) M carbachol and 9.1 with 10(-9) M cholecystokinin (both p less than 0.01). Thus, basal and secretagogue-stimulated pepsinogen secretion appear independent of acid secretion in intact guinea pig mucosa.

Animals↗
PubMed1988

Characteristics of the spontaneous gastric endocrine tumor of mastomys.

Mastomys is a rodent which has been reported to develop spontaneous antral endocrine tumors with acid hypersecretion and duodenal ulceration. This study documents the establishment of a breeding colony and the characterization of the tumors and their possible secretagogues. Parietal cell secretory characteristics were studied using isolated gastric glands (IGG) of both normal (n = 5) and tumor-bearing animals. Tumors (n = 6) and control gastric tissue samples were examined by light transmission microscopy and immunohistochemistry. Gastrin was measured by radioimmunoassay in both plasma and tissue. IGG were prepared by collagenase dispersion and acid sequestration assessed by [14C]AP accumulation. Secretory mechanisms of this species were identified by establishment of a histamine dose-response curve and use of 8-bromo-cAMP. Receptor and proton pump inhibitions were assessed using cimetidine (10(-5)M) and the H/K ATPase inhibitor omeprazole (10(-5]. Both reduced [14C]AP accumulation significantly (P less than 0.05). 8-Bromo-cAMP and histamine significantly stimulated [14C]AP accumulation (P less than 0.05). Although parietal cells were substantially increased in tumor animals as compared to controls, the physiological parameters of acid secretion appeared normal in both and were comparable to other species which have been studied. Tumors were Grimelius positive and contained diffuse electron-dense granules. Immunohistochemistry was negative for gastrin, bombesin, serotonin, neuron-specific enolase, calcitonin, and pancreatic polypeptide. Tumor histamine-like immunoreactivity was, however, positive. Normal stomach contained 1001 +/- 185 compared to less than 0.5 pmole/g gastrin in tumors. Plasma gastrin was normal in both groups (29 +/- 5) as compared to 26 +/- 8 pmole/liter. This study characterizes a spontaneous gastric endocrine tumor which is associated with apparent parietal cell hyperplasia and reports of increased acid secretion and duodenal ulceration. The observations are consistent with the elaboration by the tumor of a nongastrin acid-trophic secretagogue.

Aminopyrine↗
PubMed1988

Gastric somatostatin release: evidence for direct mediation by calcitonin gene-related peptide and vasoactive intestinal peptide.

It has previously been demonstrated that somatostatin (SRIF) directly inhibits parietal cell secretion. However, the significance of SRIF as a paracrine agent and mechanisms of local gastric SRIF release are not clear. Vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) are neuropeptides which have been localized in the gastric fundus and have been demonstrated to inhibit gastric acid secretion in vivo. The present study examines the hypothesis that CGRP and VIP act via the release of gastric fundic SRIF. The study utilized rabbit isolated gastric glands prepared by collagenase digestion. Glands were incubated alone, or with 10(-10)-10(-6) M CGRP or 10(-10)-10(-6) M VIP for 30 min. Supernatant SRIF was measured using a specific radioimmunoassay. Unstimulated SRIF release was 101 +/- 16 fmole/ml. CGRP (10(-7) and 10(-6) M) and VIP (10(-7) and 10(-6) M) resulted in significant SRIF release. The maximum release of SRIF by CGRP (506 +/- 113 fmole/ml) was significantly greater than that by VIP (293 +/- 33 fmole/ml) (P less than 0.05). However, both these concentrations of SRIF are comparable to the ID50 concentration (4.5 X 10(-10) M) for SRIF inhibition of acid secretion by isolated parietal cells as assessed by [14C]aminopyrine accumulation. These results are consistent with the hypothesis that CGRP and VIP inhibition of acid secretion may be mediated, at least in part, by the local release of SRIF from the gastric fundus. These data further support the significance of paracrine interactions in the modulation of cellular secretory function.

Animals↗
PubMed1988

Lack of peptide YY immunoreactivity in adenomatous colonic polyps: evidence in favor of an adenoma-carcinoma sequence.

The aim of endoscopic polypectomy is to prevent colorectal cancer, as it is assumed that most, if not all, large bowel cancers are derived from adenomatous polyps. While it is now recognized that colonic endocrine cells, like other mucosal epithelial cells, have an endodermal origin, they are relatively sparse components of large bowel tumors. Peptide YY (PYY) is the most abundant endocrine regulatory peptide localized to the distal bowel. Endocrine cells, like the other cells of the mucosal epithelia, are derived from a common stem cell in the base of the crypts. The presence of endocrine peptides may thus be viewed as a marker for cellular differentiation in the gut. PYY was therefore measured in colonic carcinomas and adenomatous polyps, as its absence would be evidence in favor of genetic alterations in epithelial stem cell maturation. PYY concentrations in extracts of surgically removed colonic carcinomas (n = 22) from all regions were very low compared with those of adjacent normal bowel. Similarly, PYY concentrations in extracts of polyps (n = 39) obtained during endoscopic polypectomy were also very low when compared with those of adjacent normal mucosa. These varied between 1 and 11% of the normal epithelial content, depending upon the region. Low PYY levels appeared to reflect the malignant potential of these lesions: highest in tubular polyps, lower in villous polyps, and lowest in carcinomas. The very low concentrations of PYY in adenomatous polyps, like those of colonic cancer, are consistent with epithelial dysplasia and the incomplete formation of mucosal endocrine cells. These findings support the hypothesis of an adenoma to carcinoma sequence in colonic cancer.

Adenoma↗
PubMed1988

Intramural distribution of regulatory peptides in the sigmoid-recto-anal region of the human gut.

The distribution of regulatory peptides was studied in the separated mucosa, submucosa and muscularis externa taken at 10 sampling sites encompassing the whole human sigmoid colon (five sites), rectum (two sites), and anal canal (three sites). Consistently high concentrations of VIP were measured in the muscle layer at most sites (proximal sigmoid: 286 (16) pmol/g, upper rectum: 269 (17), a moderate decrease being found in the distal smooth sphincter (151 (30) pmol/g). Values are expressed as mean (SE). Conversely, substance P concentrations showed an obvious decline in the recto-anal muscle (mid sigmoid: 19 (2.0) pmol/g, distal rectum: 7.1 (1.3), upper anal canal: 1.6 (0.6)). Somatostatin was mainly present in the sigmoid mucosa and submucosa (37 (9.3) and 15 (3.5) pmol/g, respectively) and showed low, but consistent concentrations in the muscle (mid sigmoid: 2.2 (0.7) pmol/g, upper anal canal: 1.5 (0.8]. Starting in the distal sigmoid colon, a distinct peak of tissue NPY was revealed, which was most striking in the muscle (of mid sigmoid: 16 (3.9) pmol/g, upper rectum: 47 (7.8), anal sphincter: 58 (14)). Peptide YY was confined to the mucosa and showed an earlier peak (upper sigmoid: 709 (186) pmol/g, mid-distal sigmoid: 1965 (484)). A clear differential distribution of regulatory peptides was thus shown in the region studied. A possible role is suggested for NPY and VIP containing nerves in the effector control of the human internal anal sphincter.

Aged↗
PubMed1988

Further characterisation of the 'ileal brake' reflex in man--effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY.

Previous studies have shown that ileal infusion of partially digested triglyceride inhibits jejunal motility. The partial digest used in those studies contained a mixture of glycerol, free fatty acid, mono-, di-, and triglycerides. In Part I of the present study we have separately infused emulsions containing either glycerol 3.1 g (n = 6), oleic acid 9.6 g (n = 6), triolein 10 g (n = 12), or medium chain triglycerides 10 g (n = 6) into the ileum and have recorded the effect this has on jejunal motility. Five further subjects received infusions of partial hydrolysates of corn starch 10 g and lactalbumin 7 g. Marked inhibition of jejunal pressure wave activity was seen after all three lipid infusions, per cent activity falling from a control of 37.7 (7.7) to 6.2 (2.1) and 22.4 (8.2)% 30 min after completing the oleic acid and triolein infusions respectively, and from a control value of 39.5 (4.1) to 17.7 (4.7) after MCTs (all p less than 0.05). No significant fall occurred after infusion of glycerol, protein or carbohydrate. All three lipid infusions raised plasma concentrations of neurotensin, enteroglucagon and peptide YY equally effectively, although only the rise in peptide YY correlated significantly with the inhibition of jejunal pressure wave activity (r = 0.80, n = 6, p less than 0.05). In Part II of this study six subjects received a 3 ml/min jejunal infusion of an isotonic carbohydrate saline solution followed after three hours by a similar infusion of a partial digest of lipid. During each infusion flow and transit time was measured by marker and dye dilution. Jejunal infusion of the carbohydrate-saline solution was associated with low jejunal flow, 4.7 (1.0) ml/min and a mean transit time through the 50 cm study segment of 36.5 (7.1) min. By contrast jejunal infusion of partially digested triglyceride was associated with a markedly increased flow, 9.0 (1.2) ml/min, a fall in mean transit time to 20.3 (2.6) min and significant rises in pancreaticobiliary secretions. Jejunal triglyceride also increased the incidence of prolonged high amplitude jejunal pressure waves in four of six subjects. These studies suggest that there are important differences in the jejunal response to ileal versus jejunal lipid. While long and median chain free fatty acids infused into the ileum exert an inhibitory effect on jejunal motility, when infused directly into the jejunum partially digested triglyceride accelerates transit, increases jejunal flow and subtly alters the pattern of jejunal contractions.

Adult↗
PubMed1988

Prostaglandin E analogue inhibition of intrinsic factor release.

In many mammalian species (including humans) the parietal cell secretes both acid and intrinsic factor (IF). The aim of this study was to examine the direct effect of prostaglandin E analogues on basal and stimulated IF release in isolated, enriched rabbit parietal cells. The effects of graded concentrations (10(-12) to 10(-6) M) of 16,16-dimethyl prostaglandin E2 (DMPGE2) and 16-methyl,16-hydroxyl prostaglandin E1 (misoprostol) on submaximal histamine-stimulated (10(-6) M) secretion were tested. Both analogues failed to alter basal release of IF or aminopyrine accumulation (indirect measure of acid secretion). Increasing concentrations of DMPGE2 resulted in a dose-dependent inhibition of IF release (22 +/- 8% decrease at 10(-9) M; p less than 0.05) and a maximal effective response at 10(-7) M (54 +/- 9%; p less than 0.005). Dose-dependent inhibition of IF secretion was also observed with increasing concentrations of misoprostol, with a 22 +/- 7% decrease at 10(-9) M (p less than 0.05) and maximal effective inhibition at 10(-6) M (47 +/- 8%; p less than 0.01). Misoprostol and DMPGE2 inhibition of acid secretion paralleled IF release. Prostaglandin analogues appear to block IF release potently in histamine-stimulated parietal cells.

Alprostadil↗
PubMed1988

Chronic pancreatitis and diabetes mellitus: plasma and gastroduodenal mucosal profiles of regulatory peptides (gastrin, motilin, secretin, cholecystokinin, gastric inhibitory polypeptide, somatostatin, VIP, substance P, pancreatic polypeptide, glucagon, enteroglucagon, neurotensin).

A disturbed intraduodenal milieu and pancreatic scarring in advanced chronic pancreatitis (CP) may lead to changes of gut and pancreatic hormones. In the present study, the gastroduodenal mucosal content of several regulatory peptides was determined in 8 patients with severe calcific CP and 8 healthy volunteers. In addition, hormone release into the bloodstream was estimated after intraduodenal acid/glucose stimulation in the control subjects and 8 CP patients each with or without secondary diabetes mellitus (DM), and in 8 patients with juvenile DM, so that disturbed gut hormone release could be attributed either to CP or DM. While VIP release into the circulation was similar in all participants, mucosal levels of VIP and substance P were significantly elevated in the duodenal bulb and descending duodenum of CP patients. The somatostatin content of gastroduodenal mucosa in CP was at least as high as in normals. Gastrin was significantly more abundant only in the duodenal bulb of CP patients, while plasma gastrin was normal. Duodenal CCK concentrations tended to be elevated in the duodenal bulb, but not significantly. The release of secretin seemed to be higher in type-1 diabetics than in CP patients. The mucosal pattern of GIP was nearly identical in CP patients and controls. Compatible with this finding, the GIP release did not show any peculiarities in CP with or without DM or in DM. Basal and stimulated plasma levels of motilin were abnormally high in CP. Pancreatic polypeptide plasma levels were normal in DM, but significantly reduced in CP, especially in CP with DM. Fasting PP and stimulated pancreatic enzyme outputs were linearly related.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Pancreastatin: a novel peptide inhibitor of parietal cell secretion.

Pancreastatin is a recently identified 49-amino-acid peptide found in gastrointestinal tract and gastric mucosa. Its biologic effects on gastric function are unknown. The aim of this study was to determine the effects of pancreastatin [33-49] (the synthetic C-terminal fragment) on acid secretion and somatostatin release in vitro. Isolated rabbit gastric glands were prepared by means of collagenase digestion. Acid secretion was assessed indirectly with use of 14C-aminopyrine (AP) uptake by glands, and somatostatin release from D cells was measured with radioimmunoassay. Pancreastatin alone (10(-10) to 10(-6) mol/L) had no effect on 14C-AP uptake compared with unstimulated glands. In contrast, pancreastatin inhibited with histamine-(10(-6), 10(-5) mol/L; p less than 0.005) and carbachol-(10(-5), 10(-4) mol/L; p less than 0.001) stimulated 14C-AP uptake in a dose-dependent manner. Neither forskolin-(10(-6), 10(-4) mol/L; p greater than 0.50) or 8-Br-cAMP-(10(-5), 10(-4) mol/L; p greater than 0.30) stimulated 14C-AP uptake were influenced by pancreastatin. Pancreastatin had no effect on somatostatin release from glands. These data suggest that pancreastatin probably acts at receptor or membrane level, inhibiting both histamine- and carbachol-stimulated 14C-AP uptake. These effects are not mediated by D cell somatostatin release. It is possible that pancreastatin acts as a paracrine or endocrine inhibitory regulator of parietal cell secretion.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Hypergastrinaemia of sheep infected with Haemonchus contortus.

Radioimmunoassay of plasma gastrin has shown that a hypergastrinaemia occurs in yearling sheep, after infection with 10(6) infective third stage larvae of Haemonchus contortus. Plasma gastrin concentrations began to rise two to four days after infection, that is, at about the same time as, or slightly before, the abomasal pH was observed to increase.

Abomasum↗
PubMed1987

Comparison of effects of ingested medium- and long-chain triglyceride on gallbladder volume and release of cholecystokinin and other gut peptides.

In a double-blind, crossover study of the effect of ingested medium-chain triglyceride (MCT) and long-chain triglyceride (LCT) in six normal subjects, the gallbladder did not contract after ingestion of MCT but instead had significantly increased in volume at 2 hr after the meal. Plasma cholecystokinin (CCK) increased after the MCT meal, but gastrin, motilin, pancreatic polypeptide (PP), and GIP were unaffected. The long-chain triglyceride meal evoked a brisk and sustained gallbladder contraction, higher levels of CCK, and a significant increase in plasma PP and GIP levels.

Adult↗
PubMed1987

Prostaglandin inhibition of acid is cAMP dependent.

Prostaglandin E (PGE) potently inhibits acid secretion stimulated by histamine, but not by acetylcholine or gastrin, and is accompanied by decreased intracellular cAMP. Adenylate cyclase receptor systems are composed of three complex proteins: cell receptor, nucleotide binding protein, and the catalytic subunit. The exact mechanism of PGE interaction with this complex remains unclear and elucidation of this site of action is the purpose of this study. We utilized molecular probes directed at the various components of adenylate cyclase. Cholera toxin alters the stimulatory subunit of the nucleotide binding proteins (Ns), rendering it resistant to normal deactivation, whereas N-ethylmaleimide (NEM) blocks the inhibitory subunit (Ni). Forskolin acts as a direct activator of the catalytic subunit of adenylate cyclase and 8-bromo-cAMP acts as a cyclic AMP mimetic. We measured in vitro acid secretion in isolated parietal cells by the assessment of [14C]aminopyrine (AP) accumulation. The PGE1 analog (miso) and the PGE2 analog (DMPG) were incubated in graded doses (10(-11) to 10(-6) M) with histamine (10(-6) M). Miso (10(-7) M) reduced AP accumulation to 21 +/- 8% of histamine alone (100%) and DMPG (10(-6) M) reduced AP to 61 +/- 9% (P less than 0.005 for both). AP accumulation stimulated by 8-Br-cAMP (10(-6) M) and forskolin (10(-6) M) was not significantly affected by either PGE analog (P greater than 0.05) suggesting that the site of PGE interaction is proximal to the activation of the catalytic subunit.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Somatostatin and analogs lack splanchnic vasoconstrictive effects in anesthetized pigs.

Due to an apparently selective vasoconstrictive effect on the splanchnic circulation, somatostatin (SRIF) has been advocated for the treatment of variceal hemorrhage. The present study was designed to compare and contrast the systemic and splanchnic hemodynamic effects of SRIF and two of its long-acting analogs (SMS 201,995 and L 363,568) with those of Pitressin. Anesthetized pigs were subjected to laparotomy for placement of an electromagnetic flowmeter on the main trunk of the superior mesenteric artery (SMA). Systemic hemodynamic parameters of arterial blood pressure and cardiac output were monitored with thermodilution catheters. Portal venous blood was collected for measurement of plasma levels of SMS 201,995 and L 363,568 and for determination of gastrin levels during infusion of the latter analog. Experimental drugs were administered via an aortic cannula in a range (5-10 mg/kg bolus and 5-10 mg/kg/min continuous infusion) of dosages. At the higher dosages, SRIF, SMS 201,995, and L 363,568 decreased SMA blood flow (mean% +/- SD) 5.6 +/- 2.2, 1.6 +/- 4.4, and 8.0 +/- 3.8 after 10 min. None of the values achieved significance when compared to variation in baseline determinations. Pitressin (0.25 units, intravenously) produced a consistent and highly significant (P less than 0.001) reduction-in SMA flow after 5 min. Pharmacologic levels of SMS 201,995 and L 363,568 were reliably achieved in portal blood and the latter produced significant reduction (P less than 0.05) in portal venous levels of gastrin. SRIF and its long-acting analogs produced no significant splanchnic nor systemic hemodynamic effects in this model.

Anesthesia↗