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S R Bloom

Publications and source records attributed to S R Bloom.

At least 811 records · Page 45Linked to original sources
PubMed1984

Peptide histidine isoleucine: a secretagogue in human jejunum.

Peptide histidine isoleucine (PHI) is a newly discovered peptide from porcine intestine, which has sequence homologies with VIP, an established intestinal secretagogue. To study the effects of PHI in human jejunum, natural porcine PHI was infused intravenously at 10.7 +/- 1.7 pmol/kg/min (mean +/- SEM) in normal volunteers during steady state perfusion of the jejunum with an isotonic bicarbonate-electrolyte solution. Plasma PHI concentrations rose to 279 +/- 26 pmol/l (mean +/- SEM) in the first 20 minutes of the infusion reaching 417 +/- 45 at 40 minutes. At these concentrations PHI induced a net secretion of chloride and sodium and either decreased net absorption or increased net secretion of fluid and potassium, while bicarbonate transport remained unaffected. Peptide histidine isoleucine is a potent jejunal secretagogue in man.

Adult↗
PubMed1984

Effect of peptide histidine isoleucine on water and electrolyte transport in the human jejunum.

Peptide histidine isoleucine, a 27 amino acid peptide with close amino acid sequence homology to vasoactive intestinal peptide and secretin, is distributed throughout the mammalian intestinal tract, where it has been localised to intramural neurones. An intestinal perfusion technique has been used to study the effect of intravenous peptide histidine isoleucine (44.5 pmol/kg/min) on water and electrolyte transport from a plasma like electrolyte solution in human jejunum in vivo. Peptide histidine isoleucine infusion produced peak plasma peptide histidine isoleucine concentrations in the range 2000-3000 pmol/l, flushing, tachycardia and a reduction in diastolic blood pressure. Peptide histidine isoleucine caused a significant inhibition of net absorption of water, sodium, potassium and bicarbonate and induced a net secretion of chloride, these changes being completely reversed during the post-peptide histidine isoleucine period. These findings suggest that endogenous peptide histidine isoleucine may participate in the neurohumoral regulation of water and electrolyte transport in the human jejunum.

Adult↗
PubMed1984

Gastrointestinal regulatory peptide storage granule abnormalities in jejunal mucosal diseases.

The mucosal concentrations of seven regulatory peptides and the density properties and integrity of their storage granules have been studied in mucosal biopsies from the human jejunum in eight gastrointestinal disease states and compared with normal controls. In diseases with associated mucosal inflammation (coeliac disease, Crohn's disease with jejunal involvement, postinfective tropical malabsorption, and common variable immunodeficiency) there was a selective increase in fragility of the gastric inhibitory polypeptide (GIP) and somatostatin storage granules. The gastrin, motilin, enteroglucagon, secretin, and vasoactive intestinal polypeptide granules had normal properties in these conditions. In diseases in which diarrhoea occurred in the absence of changes in jejunal mucosal histology (irritable bowel syndrome, pancreatic insufficiency, jejuno-ileal bypass for morbid obesity, and purgative abuse) there were no abnormalities of the storage granules. Increased mucosal concentrations of all peptides except vasoactive intestinal polypeptide (VIP) were found in coeliac disease and selective increases of VIP found in Crohn's disease, motilin in the irritable bowel syndrome and gastrin and GIP in pancreatic insufficiency. It is suggested that the storage granule abnormalities in the diseases with abnormal mucosal histology are secondary to the inflammatory changes.

Gastric Inhibitory Polypeptide↗
PubMed1984

VIP-, substance P- and met-enkephalin-immunoreactive innervation of the human gastroduodenal mucosa and Brunner's glands.

VIP-, substance P- and met-enkephalin-containing innervation of the human gastroduodenal mucosa and Brunner's glands was studied by immunocytochemistry on whole mount tissue preparations. A dense VIP-containing nerve supply was found around fundic and pyloric glands, while the few and scattered substance P-immunoreactive fibres tended to run across the full thickness of the gastric mucosa. In the duodenum, both VIP and substance P were present in a striking nerve network in the villi as well as in the muscularis mucosae and around blood vessels. Both peptides were also immunostained in nerve bundles and neuronal perikarya between the lobules of Brunner's glands, while only very few fibres reached the proximity of acinar cells. Met-enkephalin-immunoreactivity was detected in a small number of nerve fibres, virtually confined to the basal parts of the mucosa and to the duodenal submucous plexus.

Duodenum↗
PubMed1984

Neuropeptide tyrosine (NPY): a newly discovered peptide is present in the mammalian respiratory tract.

Neuropeptide tyrosine (NPY), a newly discovered peptide known to modulate blood vessel diameter and smooth muscle tone, has been found in many mammalian organs. Its distribution is similar to that of sympathetic nerve fibres and NPY immunoreactivity has been found in noradrenergic ganglion cells. In a study of the respiratory tract of four mammalian species--man, cat, guinea pig, and rat--NPY immunoreactivity has been localised to nerve fibres. NPY immunoreactive nerve fibres were found in the adventitia of blood vessels and in the airway smooth muscle. Its distribution was strikingly similar to that of sympathetic nerve fibres as demonstrated by dopamine-beta-hydroxylase antibodies. The mean (SD) concentrations of NPY in the guinea pig respiratory tract, as determined by radioimmunoassay of tissue extracts, were: upper trachea 3.3 (0.7), lower trachea 2.0 (0.5), and major bronchus 3.5 (1.1) pmol/g. During developmental studies in man NPY immunoreactive nerve fibres were first observed at 20 weeks' gestation in the trachea, and fibres gradually extended down into the intrapulmonary airways after birth. NPY immunoreactive nerve fibres have a distribution and developmental pattern similar to that of sympathetic nerve fibres in the respiratory tract. The finding of NPY immunoreactivity in nerve fibres in the mammalian respiratory tract adds to the growing number of peptides having potent biological actions found in this organ, and shows that the lung possesses a rich peptidergic system, which may influence pulmonary function.

Adolescent↗
PubMed1984

Pattern of cell proliferation and enteroglucagon response following small bowel resection in the rat.

Gut resection triggers off a complex series of adaptive changes in the remaining bowel. There is evidence that these are partly mediated by hormonal factors and enteroglucagons have been proposed as candidates for this role. It is uncertain, however, whether plasma enteroglucagon concentrations rise quickly enough to be involved in the rapid initial response or are persistent enough for chronic maintenance. Plasma concentrations of enteroglucagon were therefore estimated at varying times following gut resection and related to crypt cell production rate (CCPR), which was used as an index of cellular proliferation. 96 male Wistar rats had either 75% proximal small bowel resection or jejunal transection (controls). Groups of animals were killed at 1.5, 3, 6, 12, 24 and 48 days following operation and the plasma enteroglucagon and CCPR in the terminal ileum were estimated. Both values were markedly elevated at 1.5 days and continued to rise in a very similar manner in the resected group of rats. Gel permeation chromatography on Sephadex G-50 of plasma samples showed that the increase in plasma enteroglucagon was mainly due to an increase in a component of Kav 0.25, of similar molecular size to that of porcine glicentin. Thus the principal form of enteroglucagon, as a possible trophic hormone, does respond sufficiently quickly, and the response is maintained for long enough, to be involved throughout the adaptive process.

Animals↗
PubMed1984

Characterization of peptide histidine isoleucine-like immunoreactivity in the rat, human, guinea-pig and cat gastrointestinal tracts--evidence of species differences.

Peptide histidine isoleucine-like immunoreactivity (PHI-LI) was measured by radioimmunoassay in various mammalian ileal extracts fractionated by gel filtration and high-performance liquid chromatography (HPLC). The PHI-LI in the cat, human, guinea-pig and rat tissues were of similar molecular size, being indistinguishable from the porcine standard by gel filtration on Sephadex G-50 superfine, but significant differences were noted on HPLC. The major PHI-LI peaks of guinea-pig and rat were less retained than cat and human PHI-LI which had a similar retention time to porcine PHI. Human PHI-LI, although being chromatographically similar to porcine PHI, was immunologically different. This variation in molecular properties of PHI-LI suggests that extrapolation of experimental results of different species should be treated with great caution.

Animals↗
PubMed1984

Effects of peptide YY and neuropeptide Y on gastric emptying in man.

Neuropeptide Y (NPY) and peptide YY (PYY) are two structurally related peptides. PYY has been identified within endocrine cells and NPY within nerves of the gastrointestinal tract. Infusion of PYY at a low dose at a nominal rate of 2 pmol/kg/min resulted in an increment of 59.2 +/- 7.1 pmol/1 in plasma concentration and a significant delay in gastric emptying of glucose. Infusion of NPY at the same rate produced similar plasma concentrations (52.5 +/- 1.1 pmol/1) and had no significant effect on the rate of gastric emptying.

Adolescent↗
PubMed1984

High concentrations of a novel peptide, neuropeptide Y, in the innervation of mouse and rat heart.

A newly discovered bioactive peptide, neuropeptide Y (NPY), has been found in the innervation of the mouse and rat heart by immunocytochemistry, NPY-immuno-reactive nerves were very dense around the nodal tissues. They also surrounded the coronary arteries and arterioles and were found in close association with the cardiac muscle. The distribution of NPY-containing nerves paralleled that of noradrenergic fibers, demonstrated by the use of antibodies to the catecholamine-converting enzymes tyrosine hydroxylase and dopamine beta-hydroxylase. Furthermore, NPY was seen to be present in a proportion of intrinsic neurons mostly found in the atria and in close proximity to the nodal tissue. The concentrations of extractable NPY-immunoreactive material (about 150 pmol/g in whole mouse heart) by far surpasses those of the other peptides so far reported in the cardiac tissue. High performance liquid chromatography demonstrated the NPY immunoreactivity to elute in a single sharp peak, in an identical position to brain NPY.

Animals↗
PubMed1984

Neuropeptide tyrosine (NPY) immunoreactivity in norepinephrine-containing cells and nerves of the mammalian adrenal gland.

The application of immunocytochemistry at both light and electron microscopic levels has revealed neuropeptide tyrosine (NPY)-immunoreactive material to be localized to norepinephrine-containing endocrine cells in the adrenal medulla and also to varicose nerve fibers penetrating the adrenal cortex of several mammalian species, including horse, cat, rat, guinea pig and mouse. Correlative electron microscopic immunostaining has revealed that enkephalin and NPY immunoreactivities are co-localized to the same norepinephrine-containing secretory granules. High concentrations of NPY have been extracted from the mouse adrenal gland (1243.7 +/- 122.8 pmol NPY/g wet tissue; mean +/- SE). Chromatographic analysis has shown the extracted material to correspond with pure natural NPY.

Adrenal Medulla↗
PubMed1984

Distribution of peptide histidine isoleucine in the mammalian respiratory tract and some aspects of its pharmacology.

Peptide histidine isoleucine (PHI), a newly discovered neuropeptide, has been detected by RIA and immunocytochemistry in the upper respiratory tracts of the guinea pig, rat, and cat. HPLC of tracheal extracts showed a single peak of PHI immunoreactivity in each species. The immunoreactive PHI peak found in the guinea pig and rat trachea was eluted earlier than the corresponding peak from the cat, which was coeluted with the porcine PHI standard. Immunocytochemistry showed PHI immunoreactivity to be present within ganglion cells and nerve fibers in the respiratory tracts of all three species. The distribution of PHI was similar to that of vasoactive intestinal polypeptide and ganglion cells were found to contain both PHI and vasoactive intestinal polypeptide immunoreactivities. Pure natural porcine PHI induced a dose-dependent relaxation of isolated guinea pig tracheal muscle which was not blocked by antagonists to catecholamines, histamine, 5-hydroxy-tryptamine, and acetylcholine. PHI may thus be one of the local factors in respiratory control.

Animals↗
PubMed1984

The metabolism of intravenously infused neurotensin in man and its chromatographic characterization in human plasma.

The metabolism of iv infused neurotensin (NT) was studied and its disappearance half-time compared with that of infused N-terminal octapeptide of NT 1-8 in six normal subjects by RIA with antisera directed against the C- and N-terminal regions of the NT molecule. The disappearance half-time of NT in circulating plasma was 1.4 min measured with the C-terminal antibody and 6.0 min measured with the N-terminal antibody. The disappearance half-time of NT 1-8 was 30 min measured with the N-terminal antibody. Gel filtration and high pressure liquid chromatographic analysis indicated that a substantial amount of immunoreactive NT in the plasma of subjects infused with synthetic NT was eluted at the NT 1-8 position and a lesser amount of plasma NT-like immunoreactivity was eluted with synthetic NT. These findings suggest that NT is readily metabolized in the circulation to NT 1-8. A significant rise in the mean plasma concentration of pancreatic polypeptide was produced by NT, but not by NT 1-8, infused at 2.4 pmol kg-1 min-1. No changes in the mean plasma concentrations of insulin, glucose, or cholesterol were demonstrated during either infusion. The present study suggests that the rapid degradation of NT in man to its N-terminal metabolite may be one of the mechanisms for its bioinactivation in plasma.

Adult↗
PubMed1984

Distribution of immunoreactive growth hormone-releasing hormone in the human brain and intestine and its production by tumors.

A recently developed RIA for human pancreatic tumor GH-releasing hormone (hpGRH1-44NH2) was used to investigate its distribution in the human gastrointestinal tract and brain, and to determine the incidence of its production by tumors. GRH-immunoreactivity (GRH-IR) was present in several regions of the human brain, the highest concentration occurring in the hypothalamus, septum, and substantia inominata. In the gastrointestinal tract GRH-IR was present in the upper intestine, where it was confined to the epithelial mucosa. Approximately one third of all tumors examined (35 out of 97) contained significant amounts of GRH-IR. Gel chromatography of brain and intestinal extracts, and of several tumors, revealed the presence of two molecular forms of GRH-IR, one coeluting with the synthetic hpGRH1-44 amide standard (and also hpGRH1-40) and another eluting significantly later. The earlier eluting GRH-IR peak was found to be similar to the synthetic hpGRH1-44 NH2 and hpGRH1-40 on high pressure liquid chromatography analysis.

Adult↗
PubMed1984

Effect of hypothalamic neuropeptides on corticotrophin release from quarters of rat anterior pituitary gland in vitro.

The effect of six hypothalamic peptides on the basal release of ACTH and that induced by arginine vasopressin (AVP) or by ovine corticotrophin releasing factor (oCRF) from fragments of the rat anterior pituitary gland incubated in vitro was investigated. Dose-response curves to AVP and to oCRF were obtained, and the response to a low dose of oCRF was potentiated by a low dose of AVP. Basal release of ACTH was not affected by any of the peptides in concentrations in the range 10(-12) to 10(-6) mol/l, and only substance P (SP) and somatostatin (SRIF) inhibited significantly the response to oCRF in a dose-related manner. The responses to a range of doses of oCRF or AVP were reduced by 10(-8) and 10(-6) mol SP or SRIF/l, and to a greater extent by the higher dose. Except in the case of 10(-6) mol SRIF/l on the response to AVP, the response was not further diminished by preincubation of the tissue with the peptide before the stimulating agent was added. The inhibition of the responses to AVP or oCRF by 10(-9) mol SP/l was not potentiated by its combination with either 5 X 10(-10) or 10(-8) mol SRIF/l; the inhibitory effects were merely additive. The results suggest that although SRIF and SP are able to modulate the release of ACTH from the anterior pituitary gland, they do so only at a high concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1984

Effects of tactile and electrical stimuli upon release of vasoactive intestinal polypeptide in the mammalian penis.

Plasma levels of vasoactive intestinal polypeptide (VIP) in the corpora cavernosa penis and dorsal penile veins greatly exceeded those measured in the limb or caudal veins during anaesthesia in various mammals (Bennett's wallaby, Barbary sheep, cheetah, puma, sooty mangabey, pigtail macaque and chimpanzee). Tactile stimulation of the penis immediately before or during collection of blood samples resulted in an increase. In the wallaby, VIP levels (mean +/- S.E.M.) in blood samples collected from the flaccid penis in the absence of tactile stimulation were very low (0.6 +/- 0.5 pmol/l). A 36-fold increase in VIP occurred after manual extension of the flaccid penis (24.8 +/- 3.2 pmol/l) or during manually stimulated erections (25.1 +/- 1.7 pmol/l). Electrical stimulation of erection produced no significant increase in VIP levels (2.3 +/- 0.9 pmol/l) unless accompanied by tactile stimulation (17.5 +/- 1.4 pmol/l). These studies provide the first demonstration that sensory feedback from the penis plays an important role in regulating vasoactive intestinal polypeptidergic activity. Since VIP is a potent vasodilator its release due to tactile stimuli during copulation may play a role in the maintenance of penile erection.

Acinonyx↗
PubMed1984

Glucose-dependent insulinotropic polypeptide augmentation of insulin. Physiology or pharmacology?

Glucose-dependent insulinotropic polypeptide (GIP) is said to be a major physiologic factor in the augmentation of the insulin response to oral glucose. Whether GIP promotes insulin release at physiologic concentrations of glucose or GIP, however, is questionable. To investigate this further, volunteers were infused with 10, 20, or 40 g intravenous (i.v.) glucose, with or without simultaneous GIP infusion, to produce plasma levels of GIP or glucose similar to those seen after oral glucose. The effect of 40 g i.v. glucose with three times the original dose of GIP was also investigated. No significant enhancement of glucose-stimulated insulin secretion was seen when GIP was infused with 10 or 20 g i.v. glucose; however, with 40 g a doubling of the insulin response occurred. The higher dose of GIP caused a further increase in insulin response (30-min increment, 972 +/- 191 pmol/L; compared with glucose alone, 356 +/- 100 pmol/L, P less than 0.01; and compared with low GIP, 602 +/- 247 pmol/L, P less than 0.02). The glucose increment after the 40-g i.v. dose was +9.2 mmol/L. The concentration of GIP and glucose required to produce significant potentiation of the insulin response appears to be in the pharmacologic, rather than physiologic, range.

Adult↗