Biomedical subjects

M A Ghatei

Publications and source records attributed to M A Ghatei.

At least 235 records · Page 13Linked to original sources

PubMed1989

Novel peptide pancreastatin: its occurrence and codistribution with chromogranin A in the central nervous system of the pig.

The distribution of pancreastatin immunoreactivity was investigated in porcine brain, spinal cord, dorsal root ganglia, and pituitary. In the brain, immunoreactive cell bodies were present in many areas including the cortex, basal ganglia, hippocampus, thalamus, hypothalamus, mesencephalic reticular formation, cerebellum, and medulla oblongata. Immunoreactive fibres were most abundant in the globus pallidus, stria terminalis, entopeduncular nucleus, hippocampus, and in the substantia nigra. In the spinal cord, immunoreactive cells were found in laminae IV-IX. Immunoreactive fibres were concentrated in the dorsal horn. Pancreastatin immunoreactivity was localised to fibres and small cells (5-10% of the total) in the dorsal root ganglia. In the posterior pituitary, many immunoreactive fibres were present and in the anterior lobe subsets of gonadotrophs and thyrotrophs were pancreastatin-immunoreactive. The localisation of pancreastatin showed a parallel distribution with chromogranin A. Coexistence of pancreastatin with calcitonin gene-related peptide (CGRP) immunoreactivity in cell bodies in the spinal cord, including motoneurones, and with CGRP or galanin immunoreactivities in dorsal root ganglion cells was also noted. The differential pattern of pancreastatin immunostaining was reflected in the extractable levels of peptide with highest concentrations in the cortex (55.8 +/- 6.0 pmol/g wet weight, mean +/- S.E.M.), thalamus (60.0 +/- 5.0 pmol/g), hypothalamus (54.4 +/- 6.5 pmol/g), and anterior pituitary (2,714 +/- 380 pmol/g). Characterisation of pancreastatin immunoreactivity in the hypothalamus and pituitary by gel permeation and high-pressure liquid chromatography revealed multiple molecular forms, one of which was indistinguishable from natural porcine pancreastatin. The widespread distribution of pancreastatin immunoreactivity suggests this peptide may play a part in several neuroendocrine, autonomic, somatic, and sensory functions, and its colocalisation with chromogranin A is consistent with a precursor-product relationship.

Animals↗

PubMed1989

Formation of endothelin by cultured airway epithelial cells.

Immunoreactivity to endothelin was detected in conditioned culture medium from both canine and porcine tracheal epithelial cells. Gel permeation chromatography and fast protein liquid chromatography were used to confirm the identity of the endothelin. The two peaks demonstrated on fast protein liquid chromatography co-eluted with endothelin 1 and endothelin 3 respectively.

Animals↗

PubMed1989

In vivo and in vitro effects of amylin and amylin-amide on calcium metabolism in the rat and rabbit.

Amylin is a new member of the calcitonin/CGRP family: it is a 37 amino acid polypeptide which was recently isolated from amyloid deposits in pancreatic islets obtained from type II diabetics. In the present study we investigated the effect of amylin and amylin-amide on calcium metabolism in the rat and rabbit. Two main methods were used: in vivo hypocalcaemic activity was assessed by measuring plasma calcium levels after injection of the peptide in 50 g rats; and in vitro resorption of cortical bone by disaggregated rat osteoclasts was quantified by scanning electron microscopy together with image analysis. We demonstrate that amylin and amylin-amide have calcitonin-like effects: both are powerful inhibitors of osteoclastic resorption and as a consequence lower plasma calcium in both rats and rabbits. We speculate that the peptide may exert systemic or local regulatory effects on bone cells.

Amyloid↗

PubMed1989

Endothelin binding sites in porcine aortic and rat lung membranes.

High-affinity binding sites for endothelin were identified on porcine aortic and rat lung membranes. Interaction of 125I-labelled endothelin with its binding site was specific, saturable, time- and temperature-dependent but dissociation of receptor-bound ligand was minimal. Maximal binding was observed at pH 7.0 in porcine aorta and at pH 3.1 in the rat lung. Treatment of membranes with trypsin destroyed the binding site in both tissues. Porcine endothelin showed a higher affinity for receptors in both tissues compared to rat endothelin. Vasoactive peptides and Ca2+ channel antagonists did not interact with this site suggesting high specificity of binding. Analysis of saturation binding showed that the number of binding sites was 1250 +/- 104 and 1650 +/- 170 fmol/mg protein and the affinity of binding sites was 0.47 +/- 0.15 and 0.16 +/- 0.07 nM in the aorta and the lungs respectively (n = 5). Presence of protease inhibitors did not alter binding suggesting that the label was stable under the incubation conditions. This was further confirmed by HPLC. Removal of the endothelium from the aorta did not change the binding characteristics of this tissue. Ca2+ and Mg2+ ions caused an increase in binding by increasing the affinity. Binding was completely abolished in the presence of Triton and dithiothreitol. The binding sites identified in this study may be responsible for the actions of endothelin in the aorta and the lung.

Animals↗

PubMed1989

Plasma enteroglucagon, peptide YY and gastrin in rats deprived of luminal nutrition, and after urogastrone-EGF administration. A proliferative role for PYY in the intestinal epithelium?

Intestinal tissue mass was significantly reduced throughout the gastrointestinal tract (p less than 0.001) of intravenously fed (TPN) rats. Urogastrone-epidermal growth factor, (URO-EGF), reversed these changes. Although plasma enteroglucagon and gastrin levels showed a small increase with URO-EGF, this was far less than the gut tissue weight change, suggesting that it was unlikely that they were involved in modulating the proliferative response of the intestine to URO-EGF. Peptide tyrosine tyrosine (PYY) levels were however significantly increased by URO-EGF, indicating that PYY may possibly have a role in the modulation of intestinal cell proliferation.

Animals↗

PubMed1989

Diazepam binding inhibitor-like immunoreactivity(51-70): distribution in human brain, spinal cord and peripheral tissues.

We have used a specific radioimmunoassay to describe the distribution of diazepam binding inhibitor-like immunoreactivity (DBI-IR(51-70) in human post-mortem tissues. In brain, highest concentrations were found in the cerebellum, amygdala, hippocampus, hypothalamus and substantia nigra. In the spinal cord, DBI-IR(51-70) was evenly distributed. In peripheral tissues, highest concentrations were found in the liver and kidney. Chromatographic analysis revealed several molecular forms of DBI-IR(51-70) the major form being of greater molecular weight and hydrophobicity than the synthetic fragment peptide. In peripheral tissues, but not in the CNS, a small peak of immunoreactivity was indistinguishable from the synthetic peptide. DBI-IR(51-70) is therefore widespread, but tissue processing may be different.

Aged↗

PubMed1989

Altered islet amyloid polypeptide (amylin) gene expression in rat models of diabetes.

The response of the islet amyloid polypeptide gene to chronic dexamethasone treatment in adult rats was investigated. After 12 daily injections, rats were severely underweight and fasting blood glucose levels were elevated. When pancreatic mRNA was analysed, a 16-fold elevation in islet amyloid polypeptide mRNA was observed with only a four-fold increase in insulin mRNA levels. Pancreatic islet amyloid polypeptide and insulin mRNA levels were also determined 12 days after streptozotocin treatment. In these rats, which were not severely diabetic, the reduction in islet amyloid polypeptide mRNA levels was sixfold less than the reduction in insulin mRNA levels. In both these models of diabetes the ratio of islet amyloid polypeptide to insulin mRNA levels was raised. This would not be expected if the physiological role of islet amyloid polypeptide is as a simple hyperglycaemic agent opposing insulin action or release.

Amyloid↗

PubMed1989

Intravenous calcitonin gene-related peptide stimulates net water secretion in rat colon in vivo.

We have studied the effect of exogenous calcitonin gene-related peptide on net fluxes of water and electrolytes in the rat small and large intestine. In ligated intestinal loops, intravenous calcitonin gene-related peptide (CGRP) induced colonic fluid secretion but had no effect on the small intestine. Subsequently, using a single-pass perfusion technique, we observed an immediate dose-dependent secretion of water by the rat colon upon intravenous administration of CGRP. Net secretion of sodium, potassium, and chloride were also raised. The implications of these observations for the possible involvement of high circulation concentrations of CGRP in the watery diarrhea syndrome accompanying medullary thyroid carcinoma are discussed.

Animals↗

PubMed1989

Regional differences in concentrations of regulatory peptides in human colon mucosal biopsy.

The study was undertaken to examine regional differences in the concentrations of five regulatory peptides in the human colonic mucosa. Biopsies were obtained during routine colonoscopy from 33 patients whose colonic mucosa was macroscopically and histologically normal. Regulatory peptides were extracted, and measured by specific radioimmunoassays. Concentrations of three peptides that are present predominantly in endocrine cells within colonic mucosa increased significantly towards the rectum: Mean concentrations of peptide YY, enteroglucagon, and somatostatin were about three times greater in the rectum than in the cecum. However, concentrations of two peptides that are present in mucosal nerve fibers diminished significantly towards the rectum: Mean rectal concentrations of vasoactive intestinal peptide and peptide histidine methionine were both about 0.6 of mean cecal concentrations. Concentrations of all five peptides were lower in biopsies taken from colonic polyps than in normal colonic mucosa. Regional differences in colonic mucosal concentrations of regulatory peptides probably reflect differences in the physiological functions of different parts of the colon.

Adolescent↗

PubMed1989

Inhibitory effect of galanin on postprandial gastrointestinal motility and gut hormone release in humans.

Galanin was infused intravenously in 8 healthy volunteers at a dose of 40 pmol/kg.min for 1 h to investigate the pharmacologic effects of this peptide on postprandial gastrointestinal motility and gut peptide release in humans. Galanin strongly inhibited gastrointestinal motility. Gastric emptying was significantly delayed, with the time taken to empty 50% of the gastric contents increasing from 59.0 +/- 4.8 min (control infusion) to 99.3 +/- 4.7 min (galanin infusion). Mouth-to-cecum transit time increased from 67.5 +/- 6.9 to 126.3 +/- 18.5 min. Galanin potently suppressed the initial postprandial rise in plasma concentrations of glucose, insulin, peptide tyrosine tyrosine, neurotensin, enteroglucagon, pancreatic glucagon, somatostatin, and pancreatic polypeptide, but did not change gastric inhibitory polypeptide, motilin, peptide histidine methionine, and gastrin concentrations compared with control. The results indicate that an infusion of galanin has potent effects on the gastrointestinal tract in humans. The changes in motor activity in particular suggest that the local galaninergic innervation could have an important physiologic role in the control of human gastrointestinal propulsive motor activity.

Adult↗

PubMed1989

The generation of valosin-like peptides from a precursor protein in vitro as an extraction artifact.

Valosin is a 25 amino acid peptide recently isolated from the porcine gastrointestinal tract. The molecular forms of valosin-like immunoreactivity (VLIR) were examined following different tissue extraction procedures. Fractionation of tissue extracted with cold 0.1 M sodium hydroxide by Sephadex G50 gel permeation chromatography revealed a large form of VLIR (Kav = 0). Smaller forms of VLIR, Kav = 0.36 and 0.57 were obtained in tissue extracted by boiling in 0.5 M acetic acid. Acidification and boiling of the 0.1 M sodium hydroxide tissue extracts also generated smaller forms of VLIR of Kav = 0.36 and 0.57. Partially purified preparations of the large forms of VLIR extracted with sodium hydroxide could be disrupted into a smaller form of Kav = 0.57 by acidification and boiling. This smaller molecular form co-eluted with the synthetic 25 amino acid valosin standard. We conclude that valosin does not occur naturally but is an artifact generated by cleavage of a larger protein precursor upon acid extraction of tissues. Workers should be aware of the need to verify their extraction procedures when characterising novel peptides to avoid potential pitfalls such as acid/thermal cleavage of proteins.

Chromatography, Gel↗

PubMed1989

Quantitative analysis of peptide levels and neurogenic extravasation following regeneration of afferents to appropriate and inappropriate targets.

We have studied quantitatively the levels of substance P and calcitonin gene-related peptide in nerves innervating skin and muscle of rats, and examined the effects of cross-anastomosing these nerves so that they regenerate to an inappropriate target. We have also compared the ability of nerves to induce neurogenic extravasation with their peptide content. Peptide was measured by radioimmunoassay in the proximal section of ligated peripheral nerves, and neurogenic oedema was measured by determination of Evans Blue extravasation induced by either systemic capsaicin treatment or topical mustard oil application. The levels of these peptides are higher in cutaneous nerves than muscle nerves. This cannot be explained by differences in the number of fibres in the nerves studied. The levels of peptides fall when cutaneous afferents reinnervate muscle, and rise when muscle afferents reinnervate skin. We suggest that these changes occur because of some tissue-specific trophic influence arising from the tissue innervated. The ability to produce extravasation in skin is highly correlated with the substance P and calcitonin gene-related peptide levels of its innervation, even when this occurs in inappropriate nerves which do not normally produce extravasation.

Anastomosis, Surgical↗

PubMed1989

Regional distribution of chromogranin B 420-493-like immunoreactivity in the pituitary gland and central nervous system of man, guinea-pig and rat.

The distribution of chromogranin B 420-493-like immunoreactivity was investigated in the pituitary gland and central nervous system of man, guinea-pig and rat, by using two different antibodies. In man, highest chromogranin B 420-493-like immunoreactivity concentrations were found in the pituitary gland, chromogranin B 420-493 (1-17)-like immunoreactivity 74.3 +/- 8.5 (mean +/- S.E.M. pmol/g wet wt tissue) and chromogranin B 420-493 (20-38)-like immunoreactivity 2017.0 +/- 142.3, followed by the hypothalamus and substantia nigra. In the spinal cord, the highest concentration was found in the sacral dorsal area. Chromogranin B 420-493-like immunoreactivity was detected in human cerebrospinal fluid, chromogranin B 420-493 (1-17)-like immunoreactivity 376.7 +/- 77.9 and chromogranin B 420-493 (20-38)-like immunoreactivity 1174.7 +/- 259.3 pmol/l cerebrospinal fluid. Chromogranin B 420-493-like immunoreactivity was also found in high concentrations in the guinea-pig and rat pituitary glands, but very low chromogranin B 420-493-like immunoreactivity levels were present in different parts of the brain of both species. Gel permeation chromatography and fast protein liquid chromatography analysis of eight different regions of human CNS showed multiple chromogranin B 420-493-like immunoreactivity peaks. The profile of pituitary extracts was different from those of other parts of the CNS and the cerebrospinal fluid. The profiles of guinea-pig and rat pituitary on gel chromatography and fast protein liquid chromatography were different again from those of human CNS. Examination of subcellular fractionation of whole rat brain showed highest concentrations of chromogranin B 420-493-like immunoreactivity in the synaptosome fractions. Chromogranin B 420-493-like immunoreactivity release was stimulated from rat pituitary cells by high potassium ion concentrations. These findings show that (1) chromogranin B 420-493-like immunoreactivity is widely distributed throughout the pituitary gland and CNS of three mammalian species, with the highest concentration in the pituitary gland, and it is also present in human cerebrospinal fluid, and (2) the processing of chromogranin B in the pituitary gland may be different from that in the other area of the CNS, so that it is possible chromogranin B or its fragments may play a neuroeffector role in the mammalian CNS.

Adult↗

PubMed1989

Studies with endothelin-3 and endothelin-1 on rat blood pressure and isolated tissues: evidence for multiple endothelin receptor subtypes.

In an anesthetized rat, endothelin-1 (ET-1) causes a rapid, transient fall in blood pressure followed by a large, sustained rise. Rat endothelin-3 (ET-3) differs from porcine endothelin-1 (ET-1) by six amino acids and is 20 times less potent at contracting rat aortic strips. The comparative effects of ET-3 and ET-1 on blood pressure were studied in anesthetized rats in which the arterial blood pressure was continually monitored. Dose-response curves for the contraction of rat stomach strips, guinea pig ileum, and guinea pig trachea were also constructed. In the anesthetized rat, ET-3 was slightly (but not significantly) less potent than ET-1 at producing the transient blood pressure fall but was three times less potent at causing the subsequent rise. The two peptides were equipotent at contracting rat stomach strips but ET-3 was 10 times less potent at contracting the guinea pig ileum. Rat ET-3 was less potent at contracting the guinea pig trachea and had a lower maximal effect. These results suggest the existence of multiple receptor subtypes for ET.

Animals↗

PubMed1989

Galanin: hydrokinetic action on salivary glands in man.

Galanin was infused intravenously into eight healthy volunteers at a dose of 40 pmol kg-1 min-1 for 1 h to investigate the pharmacological effects of this peptide on the postprandial sialagogical response in man. Galanin significantly increased the salivary volume and the saliva output of sodium, chloride and bicarbonate compared to control saline infusion, but had no effect on the output of potassium and alpha-amylase. An increase in salivary pH was also observed. The increase in salivary volume may indicate a physiological role of galanin in the control of salivary secretion.

Adult↗

PubMed1989

Plasma enteroglucagon, gastrin and peptide YY in conventional and germ-free rats refed with a fibre-free or fibre-supplemented diet.

Germ-free rats and conventional rats were starved and then refed with either an elemental diet (Flexical), or Flexical plus 30% kaolin, or Flexical plus 30% of a fibre mixture. Plasma levels of enteroglucagon, gastrin and peptide YY (PYY) were all significantly affected by diet. Enteroglucagon and especially PYY were significantly increased by the addition of fermentable fibre to the diet, but only in the conventional, not in the germ-free rats. Gastrin was not affected by the addition of fermentable fibre, but was increased by kaolin. Enteroglucagon and PYY were, however, both very much elevated in the germ-free animals, in which there is no proliferative response to fibre. Enteroglucagon and PYY levels were similar to those usually associated with extreme hyperproliferative states, indicating that it is unlikely that these hormones are involved in the proliferative response of the gastrointestinal tract to dietary fibre, and casting doubt on their role in other responses.

Animals↗

PubMed1989

Effects of acute and chronic ethanol administration on the gastrointestinal hormones gastrin, enteroglucagon, pancreatic glucagon and peptide YY in the rat.

The effect of acute and chronic ethanol administration on the gastrointestinal hormones gastrin, enteroglucagon (EG), pancreatic glucagon (PG) and peptide YY (PYY) was studied in the rat alcohol model. Plasma levels of gastrin and PYY were not significantly changed under chronic and/or acute alcohol, while PG was stimulated by acute intraperitoneal ethanol injections in control animals as well as in chronically ethanol-fed rats (8 +/- 1 vs. 28 +/- 6 pmol/l, p less than or equal to 0.05, and 7 +/- 1 vs. 21 +/- 4 pmol/l, p less than or equal to 0.05). EG levels were significantly raised after chronic ethanol feeding (45 +/- 5 vs. 73 +/- 8 pmol/l, p less than or equal to 0.01) and even further elevated if an acute dose of alcohol was given to chronically ethanol-fed rats (73 +/- 8 vs. 168 +/- 29 pmol/l, p less than or equal to 0.05). The immunohistologically evaluated numbers of the respective hormone-producing cells were not significantly changed by alcohol feeding. The ethanol-dependent elevations of EG and PG may contribute, at least in part, to the intestinal hyper-regeneration, motility disturbances and altered glucose metabolism observed after alcohol consumption.

Animals↗

PubMed1989

Production of GAWK (chromogranin-B 420-493)-like immunoreactivity by endocrine tumors and its possible diagnostic value.

GAWK (chromogranin-B 420-493) is a 74 amino acid peptide recently isolated from human pituitaries. Using two different antibodies (directed against GAWK [1-17] and [20-38] fragments) GAWK-LI was measured in tumors from 194 patients and in the plasma of 434 patients by RIA. The highest tissue concentrations of GAWK-LI were found in pheochromocytoma (GAWK [1-17]-LI, 18,173 +/- 3,915; GAWK [20-38]-LI, 17,852 +/- 2,763 [mean +/- SEM] pmol/g wet wt tissue; n = 9), which were at least ten times higher than any other tumors producing GAWK-LI. High concentrations of GAWK-LI were also found in other types of endocrine tumors including carcinoid, medullary carcinoma of thyroid, pancreatic, and ACTH-producing lung tumors. On the other hand, low concentrations of GAWK-LI were found in nonendocrine tumors. Plasma concentrations of GAWK-LI were found to be elevated in patients with endocrine tumor, but more so in those with pancreatic tumors than with pheochromocytomas. Plasma concentrations returned to normal after successful tumor removal. Chromatographic profiles of GAWK-LI in extracts of pheochromocytomas and normal adrenals showed high molecular weight peaks that were absent in the extracts of other endocrine tumors and normal pancreas, suggesting differential tissue-specific processing. Thus GAWK-LI is produced by a variety of endocrine tumors and may serve as a plasma tumor marker, especially in patients with pancreatic endocrine tumors.

Adrenal Gland Neoplasms↗