Biomedical subjects

G H Greeley

Publications and source records attributed to G H Greeley.

At least 91 records · Page 5Linked to original sources

PubMed1989

Peptide YY inhibits the insulinotropic action of gastric inhibitory polypeptide.

Peptide YY (PYY) is released from the gut after ingestion of fat or after a meal. The purpose of this investigation was to examine the effect of PYY on gastric inhibitory polypeptide (GIP)-stimulated insulin release in conscious dogs with gastric and duodenal fistulas. In control experiments, 6 dogs received GIP (400 pmol/kg, i.v., for 1 h) and glucose (0.6 g/kg, i.v., for 1 h); the integrated insulin response over a 1-h period was 142 +/- 32.7 ng-60 min/ml. The plasma GIP levels achieved by this procedure were similar to those observed by intraduodenal infusion of Lipomul (2 ml/min), suggesting that the dose of GIP used was within the physiologic range. Intravenous infusion of three different doses of PYY (100, 200, or 400 pmol/kg.h) caused a significant inhibition of insulin release stimulated by GIP + glucose; the integrated insulin response was reduced to 105, 88, and 79 ng-60 min/ml, respectively. On the other hand, PYY (400 pmol/kg.h) had no effect on insulin secretion induced by intravenous glucose (0.6 g/kg.h) alone. These results indicate that PYY specifically inhibits the insulinotropic action of GIP and that PYY may play a negative-feedback regulatory role in the enteroinsular axis.

Animals↗

PubMed1989

Gastrointestinal peptides.

The intent of this article is to summarize the primary structures (that is, amino acid sequences) localization, primary gastrointestinal and pancreatic actions, and possible clinical relevance of the major gut peptides as well as some of the miscellaneous gut peptides. A brief overview of the general characteristics of gut peptides is presented.

Digestive System Physiological Phenomena↗

PubMed1989

[Cellular localization, half-life, and secretion of peptide YY].

Tissue and plasma concentration of peptide YY (PYY) were measured by means of a radioimmunoassay (RIA) developed in our laboratory, using a specific PYY antiserum generated in New Zealand white rabbits against synthetic PYY, and dextran-coated charcoal to terminate the assay. Cellular localization of PYY was studied immunohistochemically using the peroxidase-antiperoxidase (PAP) technique. The highest tissue concentration of PYY was found in the mucosa of the terminal ileum and colon. PYY-containing secretory granules were primarily found in the basal pole of open-type endocrine cells. Basal plasma concentration of PYY was 70 +/- 9 pg/ml and rose to 357 +/- 30 pg/ml during the IV administration of PYY at 400 pmol/kg-h. A significant correlation was found (r = 0.94, p less than 0.05) between dose of PYY (12.5, 25, 50, 100, 200, 400 pmol/kg-h, IV) and plasma concentration of PYY. The calculated half-life of PYY in plasma was 8.3 +/- 1.9 minutes. Plasma concentration of PYY during the intraduodenal administration of sodium oleate (150 +/- 20 pg/ml) or long-chain triglyceride (187 +/- 37 pg/ml) was similar to plasma concentration of PYY obtained during the IV administration of PYY at 100 pmol/kg-h. Plasma concentration of PYY raised (126 +/- 10 pg/ml) after the administration of bombesin (400 pmol/kg-h, IV). Bile enhanced release of PYY. The present study suggests a hormonal role for PYY.

Amino Acids↗

PubMed1988

Effect of aging on gastric acid secretion, serum gastrin, and antral gastrin content in rats.

The purpose of this study was to characterize the effects of aging on gastric acid secretion and on serum and antral concentrations of gastrin in rats. Young and old Fischer 344 rats were prepared with gastric fistulas. Twenty-four hours after surgery, graded doses of human synthetic gastrin-17 (SHG-17) (2, 5, 10, 20, and 40 micrograms/kg) were given intravenously in random order. Gastric secretions were collected for gastric acid measurement before and at 15-min intervals after each dose of gastrin. In a separate study, blood was collected and the stomachs were removed for antral gastrin extraction from fed young and old rats. Serum and antral gastrin was measured by radioimmunoassay. The basal and gastrin-stimulated acid secretions were significantly decreased in aged rats compared to the young rats. The basal acid output was 0.4 +/- 0.2 microeq/15 min in the aged rats and 1.5 +/- 0.5 microeq/15 min in the young. The maximal acid output stimulated by gastrin was 11.1 +/- 1.8 microeq/15 min in the aged rats and 24.2 +/- 2.8 microeq/15 min in the young. Both serum and antral concentrations of gastrin were significantly decreased in aged rats. Serum gastrin concentration was 114.8 +/- 7.4 pg/ml in the aged rats and 192.0 +/- 14.4 pg/ml in the young. Antral gastrin concentration was 3.9 +/- 0.5 micrograms/g tissue in the aged rats, which was significantly less than the concentration in the young (6.5 +/- 0.4 micrograms/g tissue). Antral gastrin content did not change with aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1988

Circadian rhythms in gastrin receptors in rat fundic stomach.

Circadian rhythmicity in the number of gastrin receptors in rat fundic mucosa was characterized and was related to the concentrations of gastrin in serum and in antrum. Male Sprague-Dawley rats were acclimated to 12 hr light alternating with 12 hr darkness. Subgroups of six rats each were killed at 4-hr intervals. Fundic mucosa was collected for measurement of gastrin receptors; serum and antral tissues were collected for measurement of gastrin levels by radioimmunoassay. Circadian periodicity in the data was determined by cosinor analyses. In both freely fed and fasted rats, gastrin receptors showed circadian variation (range 2.5-10 fmol/mg protein), as did serum gastrin concentrations (range in fed rats 195-407 pg/ml). The phasing of the intrinsic circadian variation in gastrin receptor level that was observed in the fasted rats was advanced by a few hours in fed rats. This shift is probably due to food-induced gastrin release, resulting in gastrin-mediated down-regulation of gastrin receptors, followed by up-regulation of gastrin receptors. Food-related effects were thus superimposed upon the intrinsic circadian rhythms in gastrin receptor levels, causing the circadian variation in gastrin receptor levels in the fed rats to be shifted forward compared to that in the fasted rats. No significant circadian rhythms, on the other hand, were found in concentrations of gastrin in the antrum. These results suggest that changes in sensitivity of target tissues to hormones are related to both intrinsic circadian rhythms in levels of hormone receptors and also to food-related changes in hormone-receptor levels mediated by changing serum hormone levels.

Analysis of Variance↗

PubMed1988

Regulation of the release of cholecystokinin by bile salts in dogs and humans.

The objective of these studies was to investigate the role of bile salts in the regulation of release of cholecystokinin in response to nutrients in dogs and humans. In dogs, the intraduodenal administration of a bile salt sequestrant, cholestyramine (2, 4, or 8 g/h), resulted in a dose-related enhancement of the release of cholecystokinin-33/39 and pancreatic protein secretion in response to intraduodenal administration of amino acids. Intraduodenal administration of cholestyramine alone did not affect basal levels of cholecystokinin-33/39 or pancreatic protein secretion. Total diversion of bile also significantly increased the release of cholecystokinin and pancreatic protein secretion in response to intraduodenal administration of amino acids. Replacement of the bile salt pool by intraduodenal administration of taurocholate completely reversed the enhancement effect of both cholestyramine and bile diversion. In humans, oral ingestion of cholestyramine (12 g) significantly increased the release of cholecystokinin-33/39 and gallbladder contraction in response to the oral ingestion of either a triglyceride or amino acids. These results support a physiologic role of bile salts in the negative feedback regulation of release of cholecystokinin in response to luminal nutrients.

Adult↗

PubMed1988

Peptide YY inhibits pancreatic secretion by inhibiting cholecystokinin release in the dog.

Peptide YY inhibits the pancreatic exocrine secretion (bicarbonate, water, and protein) that is stimulated by cholecystokinin, secretin, or neurotensin in the dog, but whether peptide YY inhibits the release of gut peptides that stimulate pancreatic exocrine secretion is not known. Six dogs were prepared with gastric, pancreatic, and cecal cannulas. On separate days, a single dose of sodium oleate (3, 6, 7.5, 9, 12, 15, or 18 mmol/h) was given intraduodenally for 90 min, either alone (control) or in combination with peptide YY (25, 50, 100, 200, or 400 pmol/kg.h, i.v.). We measured plasma levels of cholecystokinin-33/39, secretin, neurotensin, and peptide YY by radioimmunoassay. During infusion of peptide YY, the integrated release of cholecystokinin (3.3 +/- 0.5 ng-[0-90] min/ml) was decreased significantly (p less than 0.05) when compared with control values (5.6 +/- 0.6). Release of secretin and neurotensin was not affected. A positive correlation (p less than 0.05) was found between the release of cholecystokinin and pancreatic protein output in both control (r = 0.68) and peptide YY-treated (r = 0.67) groups. Release of peptide YY was significant after intraduodenal or intracolonic administration of sodium oleate. These studies demonstrate that inhibition of pancreatic protein secretion by peptide YY in dogs is mediated, at least in part, by an inhibition of the release of cholecystokinin.

Animals↗

PubMed1988

Peptide YY and gallbladder contraction. Studies in vivo and in vitro.

The purpose of this study was to examine the effect of peptide YY on contraction of the gallbladder in vivo and in vitro and on contraction of the sphincter of Oddi in vitro. In conscious dogs that were prepared with strain-gauge force transducers implanted in the gallbladder wall, peptide YY (400 ng/kg, bolus; 800 pmol/kg.h, infusion) did not affect the resting contractile pattern of the gallbladder, nor did it inhibit cholecystokinin-octapeptide (CCK-8)-stimulated gallbladder contraction. In contrast, the cholecystokinin antagonist proglumide (5, 10, 20, 40, or 80 mg/kg), given in vivo, inhibited CCK-8-stimulated gallbladder contraction in a dose-related manner. The highest dose of proglumide (80 mg/kg) completely abolished contraction of the gallbladder stimulated by CCK-8. In vitro studies showed that peptide YY (0.25, 0.5, or 1 microgram/ml) did not affect the resting tension of rabbit gallbladder strips, and it did not inhibit CCK-8-stimulated contraction of gallbladder strips. Proglumide (0.4, 0.8, 1.6, or 3.2 mg/ml) inhibited CCK-8-stimulated tension of gallbladder strips in a dose-related manner. Peptide YY and CCK-8 had no effect on the motility of the canine sphincter of Oddi in vitro, whereas acetylcholine caused contraction and adrenergic agonists caused relaxation. These results suggest that peptide YY and pancreatone (a peptidelike substance, extracted from ileal and colonic mucosa, that inhibits CCK-8-stimulated gallbladder contraction in vivo) do not appear to be identical.

Ampulla of Vater↗

PubMed1988

Effect of calcitonin gene-related peptide on glucose and gastric inhibitory polypeptide-stimulated insulin release from cultured newborn and adult rat islet cells.

Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide that is present in peripheral cells of islets and in nerves around and within islets. CGRP can inhibit insulin secretion in vitro and in vivo. Whether the inhibitory action of CGRP is mediated by somatostatin or by nerve terminals is, however, not known. The objective of this study was to examine the effect of CGRP on insulin secretion, using cultured newborn and adult rat islet cells which did not contain nerve terminals. In adult rat islet cells, CGRP (10(-10) to 10(-8) M) significantly inhibited glucose-stimulated and gastric inhibitory polypeptide (GIP)-potentiated insulin secretion, but in newborn rat islet cells, CGRP did not inhibit glucose-stimulated insulin secretion. Inhibition of glucose-stimulated and GIP-potentiated insulin release was dependent on the glucose concentration during the prestimulation period. CGRP did not stimulate release of somatostatin. These findings suggest that rat CGRP can act directly on beta-cells through a specific receptor that is absent in newborn rat beta-cells.

Aging↗

PubMed1988

Colocalization of calcitonin gene-related peptide and somatostatin in pancreatic islet cells and inhibition of insulin secretion by calcitonin gene-related peptide in the rat.

Calcitonin gene-related peptide (CGRP)- and somatostatin (SRIF)-containing cells were identified by immunocytochemical techniques in pancreatic islet cells of the rat. CGRP-containing cells were found primarily in the peripheral portion of the pancreatic islets. In addition, CGRP-containing cells also contained somatostatin, which identifies the islet CGRP-containing cells as D cells. In the present study, we also tested the effect of CGRP on gastrin-releasing peptide (GRP; 10(-9) M)- or cholecystokinin (CCK-8, 10(-9) M)-stimulated release of insulin from isolated rat islets in vitro. At concentrations of 10(-8)-10(-11) M, CGRP inhibited GRP- and CCK-8-stimulated release of insulin significantly when compared with GRP or CCK-8 alone. At the lowest concentration of CGRP (10(-11) M), the inhibitory effect of CGRP on CCK-8-stimulated release of insulin was statistically significant (p less than 0.05) and exceptionally potent (65-90% inhibition). We have also found that CGRP does not stimulate the release of SRIF from isolated islet cells. These findings suggest that CGRP may play a regulatory role in the release of insulin.

Animals↗

PubMed1988

A comparison of the insulinotropic and the insulin-inhibitory actions of gut peptides on newborn and adult rat islet cells.

The objective of this study was to examine the release of insulin from cultured islet cells, taken from the pancreas of newborn and adult rats, in response to gastric inhibitory polypeptide (GIP), cholecystokinin-8 (CCK-8), calcitonin gene-related peptide (CGRP), and pancreastatin. GIP (10(-9)-10(-7) M) potentiated glucose-stimulated release of insulin in a dose-dependent fashion from both newborn and adult islet cells. CCK-8 (greater than 10(-8) M) also increased glucose-stimulated release of insulin from newborn islet cells, however its effect was not significant and not as strong as that observed with adult islet cells. Culture of newborn islet cells for 3 weeks with media containing high concentrations of glucose (16.7 mM) enhanced insulin release in response to CCK-8. CGRP did not affect the release of insulin from newborn islet cells, whereas at 10(-10) M, it reduced the release of insulin from adult islet cells by 66 +/- 4%. Pancreastatin (10(-9)-10(-8) M) did not affect the release of insulin from newborn islet cells when cells were incubated with 4.2 mM glucose, whereas it stimulated the release of insulin from adult islet cells in a dose-dependent fashion. When incubated with 16.7 mM glucose, pancreastatin inhibited the release of insulin from both newborn and adult islet cells. These results indicate that newborn islet cells experience developmental changes which render them responsive to enteric peptides.

Age Factors↗

PubMed1988

Peptide YY antagonizes beta-adrenergic-stimulated release of insulin in dogs.

Peptide YY (PYY) and neuropeptide Y (NPY) are peptides of 36 amino acids that share structural homologies with pancreatic polypeptide (PP). PP is predominantly found in the endocrine pancreas. PPY is primarily found in mucosal endocrine cells of the distal ileum, colon, and rectum, whereas NPY is found in both the peripheral and central nervous systems. Previous studies indicate that these peptides can interact with the autonomic nervous system. The objective of the present experiments was to study the effect of PYY on neurally stimulated insulin release [i.e., in response to 2-deoxy-D-glucose (2-DG), a nonmetabolizable glucose analogue] in conscious dogs. Intravenous administration of PYY (100, 200, and 400 pmol.kg-1.h-1) reduced 2-DG-stimulated insulin release in a dose-dependent manner (P less than 0.05) without affecting plasma glucose levels. Administration of NPY (800 pmol.kg-1.h-1), but not PP (400 pmol.kg-1.h-1), reduced 2-DG-stimulated release of insulin (P less than 0.05). The inhibitory action of PYY on 2-DG-stimulated insulin release persisted in the presence of atropine or phentolamine treatment; however, hexamethonium alone or phentolamine plus propranolol treatment blocked the inhibitory action of PYY. Release of insulin stimulated by the beta-agonist isoproterenol was also inhibited by PYY (P less than 0.05). These results indicate that PYY can inhibit autonomic neurotransmission by a mechanism that may involve ganglionic or postganglionic inhibition of beta-adrenergic stimulation. Our findings suggest a role for PYY and NPY in the autonomic regulation of insulin release.

Animals↗

PubMed1988

Cross-reaction of two different somatostatin antisera with calcitonin gene-related peptide.

Two different anti-somatostatin antisera, R-101 and OAL-273, cross-react with rat calcitonin gene-related peptide (1-37) (CGRP). CGRP amounts, in excess of 6.25 x 10(-9) M, cross-react with R-101 in the somatostatin radioimmunoassay. CGRP amounts, in excess of 1.6 x 10(-9) M, cross-react with OAL-273. Both CGRP displacement curves are parallel to that of synthetic somatostatin (1-14). Comparison of ID50's shows that the cross-reactivity of CGRP with R-101 and OAL-273 are 0.02 and 0.1% of somatostatin, respectively.

Amino Acid Sequence↗

PubMed1988

Inhibition of gastric acid secretion by peptide YY is independent of gastric somatostatin release in the rat.

The purpose of this study was to determine whether the inhibitory action of peptide YY (PYY) on gastric acid secretion is attributable to the release of gastric somatostatin in rats. Two groups of rats (six rats/group) were anesthetized with urethane and prepared with gastric fistulas and jugular catheters. Pentagastrin (18 micrograms/kg-h) was given intravenously for 150 min to stimulate gastric acid secretion. Intravenous PYY (130 micrograms/kg-h) inhibited pentagastrin-stimulated gastric acid secretion significantly (P less than 0.05). Administration of iv PYY resulted in a 41% reduction (P less than 0.05) in pentagastrin-stimulated gastric acid secretion. In another group of anesthetized rats, administration of PYY (10(-7), 10(-8) M) failed to stimulate a release of somatostatin from the isolated-perfused rat stomach. Our findings indicate that PYY can inhibit gastric acid secretion independently of release of gastric somatostatin in the rat.

Animals↗

PubMed1988

Calcitonin gene-related peptide inhibits gallbladder contractility.

Calcitonin gene-related peptide (CGRP), a 37-amino acid peptide, is widely distributed in the gastrointestinal tract where it is colocalized with substance P. The effect of CGRP on gallbladder motility is unknown. The objective of this study was to examine the effect of CGRP on cholecystokinin-octapeptide (CCK-8) and substance P-stimulated gallbladder contraction in vivo and in vitro. In in vivo studies intragallbladder pressure was measured in response to bolus administration of CCK-8 (10(-15) to 10(-9) mol/kg) or substance P (10(-12) to 10(-7) mol/kg), either alone or with a continuous infusion of CGRP (10(-9) mol/kg/hr), in anesthetized guinea pigs. In in vitro studies the contractile force of guinea pig gallbladder muscle strips was examined in response to CCK-8 (10(-12) to 10(-7) mol/L) and substance P (10(-9) to 10(-6) mol/L), alone or with CGRP (10(-10) to 10(-6) mol/L). CGRP (10(-9) mol/kg/hr) inhibited in vivo gallbladder contraction that was stimulated by CCK-8, but not by substance P. CGRP alone produced a significant (p less than 0.05) dose-related decrease in the resting tension of gallbladder strips in vitro. CGRP (10(-6) mol/L) inhibited gallbladder muscle tension in vitro, stimulated by both CCK-8 and substance P. These studies show that CGRP can affect gallbladder motor activity by decreasing smooth muscle tone and that CGRP can antagonize the action of CCK and substance P. CGRP may be involved in the physiologic control of gallbladder emptying and refilling.

Animals↗

PubMed1988

Establishment of a human gastrinoma in nude mice.

We report the first establishment and characterization of functioning gastrinoma from a human being transplanted into nude mice. Tissue was obtained at operation from a gastrinoma liver metastasis from a patient with the Zollinger-Ellison syndrome. The tumor was implanted subcutaneously in five athymic nude mice. Serum gastrin was measured by means of radioimmunoassay in specimens of mouse blood taken before and 5 minutes after intraperitoneal injection of secretin (100 micrograms/kg). In a second experiment serum gastrin was measured 30 minutes after injection of somatostatin analogue, SMS 201-995 (300 micrograms/kg). Studies were also done in 10 control mice. At passage, the fundus of each tumor-bearing mouse was weighed and examined microscopically. The gastrinoma (tumor line, PT) has been maintained for 34 months through four passages with a tumor doubling time of 37 to 45 days. The histology is similar to the original tumor. Immunocytochemistry showed that PT contained gastrin. In two mice metastasis developed 9 months after implantation. Gastrin levels in mice bearing PT have ranged from 216 to 12,000 pg/ml. Gastrin levels of control mice ranged from 0 to 63 pg/ml. Secretin increased gastrin levels in three of five mice tested and decreased gastrin levels in two mice. Repeat secretin tests showed identical results. SMS 201-995 decreased gastrin levels from basal values. Fundic weight of mice bearing PT (397 +/- 93 mg) was significantly greater than control fundic weight (180 +/- 26 mg). Gastrinomas growing in nude mice produce physiologically active gastrin as shown by elevated serum gastrin levels and by hyperplasia of the stomach. Two distinct subpopulations of gastrinoma cells respond differently to secretin. This model should provide important information on mechanisms of growth control and on gastrin release by gastrinomas in human beings.

Adult↗

PubMed1988

Interaction of neurotensin, secretin and cholecystokinin on pancreatic exocrine secretion in conscious dogs.

The results of previous studies from our laboratory have shown that neurotensin can stimulate pancreatic secretion of bicarbonate and protein. This study was done to compare the stimulatory action of neurotensin on pancreatic exocrine secretion in conscious dogs to those of secretin and cholecystokinin (CCK). Six dogs with chronic pancreatic and gastric fistulas were given hydrochloric acid intraduodenally or CCK-8 intravenously to produce maximal bicarbonate or protein secretion. Neurotensin was then given intravenously in combination with intraduodenal hydrochloric acid or intravenous CCK-8. Incremental bicarbonate outputs in response to intraduodenal hydrochloric acid alone were measured and compared with intraduodenal hydrochloric acid plus intravenous neurotensin. Intravenous administration of neurotensin augmented pancreatic bicarbonate and protein secretory responses to a maximal dose of intraduodenal hydrochloric acid. Incremental protein responses to intravenous CCK-8 alone were measured and compared to intravenous CCK-8 plus intravenous neurotensin. Incremental bicarbonate responses to intravenous CCK-8 alone were compared with intravenous CCK-8 plus intravenous neurotensin. Similarly, intravenous neurotensin augmented pancreatic protein and bicarbonate secretory responses to a maximal dose of intravenous CCK-8. The results of this study indicate that neurotensin may stimulate pancreatic secretion of protein and bicarbonate by mechanisms which are different from those of CCK and secretin. Neurotensin apparently exerts its action through specific neurotensin receptors.

Animals↗

PubMed1988

The mechanism of the inhibitory action of neurotensin on pentagastrin-stimulated gastric secretion in dogs.

Neurotensin is a potent inhibitor of pentagastrin-stimulated gastric acid secretion. This study was done to investigate the possible role of vagal innervation and of prostaglandins on this inhibitory effect. Five dogs with gastric cannulas were infused with pentagastrin (1 microgram per kilogram of body weight each hour) for 210 minutes. In the 60 to 150 minute period, neurotensin (5.5 micrograms per kilogram of body weight each hour) was infused. Neurotensin significantly decreased pentagastrin-stimulated gastric acid output, while the simultaneous administration of indomethacin (bolus of 1 milligram per kilogram of body weight plus infusion of 0.5 milligrams per kilogram each hour) abolished the effect of neurotensin. After truncal vagotomy, the inhibitory effect of neurotensin was again studied. Since the sensitivity of the stomach to pentagastrin decreased after vagotomy, the dose of pentagastrin was doubled (2 micrograms per kilogram of body weight each hour) in order to achieve acid stimulation comparable with the levels before vagotomy. After vagotomy, neurotensin inhibited the effect of pentagastrin in a manner similar to that shown before vagotomy. The inhibitory potency of neurotensin on gastrin-stimulated gastric secretion is independent of the vagus, but requires intact synthesis for prostaglandins.

Animals↗