Biomedical subjects

M A Ghatei

Publications and source records attributed to M A Ghatei.

At least 289 records · Page 16Linked to original sources

PubMed1986

Octadecaneuropeptide, benzodiazepine ligand, -like immunoreactivity in rat central nervous system, plasma and peripheral tissues.

Using a specific radioimmunoassay we have investigated the distribution of octadecaneuropeptide (a putative endogenous ligand at the benzodiazepine receptor)-like immunoreactivity (ODN-IR) in rat brain and peripheral tissues. Highest concentrations in brain were found in the hypothalamus, cerebellum and substantia nigra. Significant concentrations of ODN-IR were found in all peripheral tissues studied and in plasma. Chromatographic analysis revealed several molecular forms; one major form, indistinguishable from the synthetic peptide, was found predominantly in peripheral tissues and in plasma, while another major form, of higher molecular weight, was found in brain, peripheral tissues and plasma. Although ODN-IR was present in the synaptosomal fraction, concentrations in the microsomal fraction were higher than for other neuropeptides studied.

Animals↗

PubMed1986

Characterization of neuromedin U like immunoreactivity in rat, porcine, guinea-pig and human tissue extracts using a specific radioimmunoassay.

Two novel bioactive peptides termed neuromedin U-8 and neuromedin U-25 have recently been isolated from porcine spinal cord but nothing is known of their occurrence and molecular forms in other species. Following gel permeation chromatography, a specific radioimmunoassay detected only a single molecular form of neuromedin U-like immunoreactivity (NmU-LI) in rat, porcine and human central nervous system and gastrointestinal tract. Only guinea pig tissue extracts revealed two molecular forms of NmU-Li. Reverse phase high performance liquid chromatographic (HPLC) analysis demonstrated that porcine NmU-LI co-eluted with synthetic neuromedin U-25 standard. Human and rat NmU-LI however, was more hydrophobic on HPLC thus indicating species differences.

Animals↗

PubMed1986

Depletion of neuropeptides during wound healing in rat skin.

The peptides substance P, calcitonin gene-related peptide and somatostatin are present in nerve fibres in mammalian, including human, skin. There is evidence that in addition to having a putative neurotransmitter role, they may be trophic agents: a study was therefore undertaken of peptide changes during wound healing in rat skin. A significant depletion of the neuropeptides was found in the region of the wound within two days, and this persisted for two weeks. A smaller and delayed depletion also occurred in intact skin of the same dermatome, but not in an adjacent dermatome.

Animals↗

PubMed1986

Regional distribution of a novel peptide (P7 of 1B236) immunoreactivity in the human central nervous system.

The regional distribution of a novel peptide (P7 of 1B236) in the human central nervous system (CNS) was examined. P7-like-immunoreactivity (p7-LI) was shown to be distributed throughout the CNS, with a chromatographic pattern closely similar to that previously described in rat. In the brain the concentrations of P7-LI were higher in the globus pallidus and substantia nigra than in any other regions. Considerable amounts of P7-L1 were also found in the cerebellum. In the spinal cord the concentration of P7-L1 was slightly higher in the ventral than in the dorsal cord, though no difference in concentration was found between cervical, thoracic, lumbar and sacral regions. The distribution pattern of this novel peptide reveals its predominance in sub-cortical motor areas. Studies of its pharmacological effects and possible role in movement disorders are awaited with interest.

Adult↗

PubMed1986

Capsaicin induces a depletion of calcitonin gene-related peptide (CGRP)-immunoreactive nerves in the cardiovascular system of the guinea pig and rat.

We have demonstrated that calcitonin gene-related peptide (CGRP) immunoreactivity is widely distributed in cardiac and perivascular nerves of the guinea pig and rat. In the guinea pig the number and distribution of CGRP-immunoreactive nerve fibres closely paralleled that of fibres containing substance P, the two immunoreactivities being found invariably to coexist in the same perivascular networks and terminals. In the rat, CGRP-immunoreactive cardiovascular nerves had a similar distribution to those containing substance P, but in contrast to the guinea pig the former were far more numerous. Marked regional variations were observed in the density of the CGRP-immunoreactive innervation in both species. The CGRP-immunoreactive content of tissue extracts was in close agreement with the immunocytochemical findings, the highest levels of CGRP occurring in the mesenteric artery (guinea pig and rat) and inferior vena cava (guinea pig). Following capsaicin treatment of adult guinea pigs and neonatal rats, there was a significant loss of CGRP-immunoreactive nerves in the two species. In the guinea pig, substance P-and CGRP-immunostained fibres were depleted to a similar extent, throughout the cardiovascular system. However, the loss of rat CGRP-immunoreactive nerves was dose-dependent and displayed considerable variation, some perivascular nerve networks appearing less susceptible than others to the action of capsaicin. The results suggest that there may be species differences in the sensitivity of CGRP-containing nerves to capsaicin treatment, but at least the majority of CGRP-immunoreactive cardiovascular nerves may be presumed to be sensory in origin.

Animals↗

PubMed1986

Calcitonin gene-related peptide immunoreactivity in afferent neurons supplying the urinary tract: combined retrograde tracing and immunohistochemistry.

The innervation of rat and guinea pig urinary tract was examined using immunohistochemistry, radioimmunoassay and True Blue retrograde tracing techniques and was further assessed following both surgical and chemical denervation experiments. Substantial amounts of calcitonin gene-related peptide-like immunoreactivity (range 20-150 pmol/g) were detected in tissue extracts and localised to nerve fibres distributed throughout the urinary tract of both species, these being concentrated in the ureter and base of the bladder. In the guinea pig, the number and distribution pattern of calcitonin gene-related peptide-like immunoreactive nerves appeared to be identical to that of substance P-containing nerves, whereas in the rat the former predominated. Seven days after injection of the fluorescent dye True Blue into tissues of the urinary tract, retrogradely labelled cells were found in the dorsal root ganglia. These cells had a segmental distribution pattern which was specific for each of the injection sites. Thus, after injection of True Blue into the left kidney hilum a single group of labelled cells were found in the ipsilateral T10-L2 dorsal root ganglia. In contrast, injection into the left ureter produced labelled cells in two separate groups of ipsilateral ganglia (T11-L3 and L6-S1). Injection into the wall of the bladder and upper urethra resulted in bilateral labelling, with most labelled cells occurring in L6 and S1 ganglia. Approximately 90% of labelled cells in T10-L3 dorsal root ganglia displayed calcitonin gene-related peptide-like immunoreactivity, but only 60% of retrogradely labelled bladder neurons in L6-S1 ganglia were immunoreactive for this peptide. Adult guinea pigs and neonatal rats injected systemically with capsaicin subsequently exhibited a marked reduction both in the amount of calcitonin gene-related peptide immunostaining and the concentration of immunoreactive material in the urinary tract, dorsal root ganglia and spinal cord. In rats treated neonatally with capsaicin, there was a significant reduction in the number of retrogradely labelled cells and a hypertrophy of the bladder. Sectioning of the pelvic and hypogastric nerves in the rat also resulted in a depletion of calcitonin gene-related peptide-like immunoreactive nerves in the bladder, whereas chemical sympathectomy appeared to have no effect. The results indicate that calcitonin gene-related peptide immunoreactivity occurs in a major proportion of afferent neurons supplying the urinary tract of the rat and guinea pig.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1986

Occurrence, distribution and ontogeny of CGRP immunoreactivity in the rat lower respiratory tract: effect of capsaicin treatment and surgical denervations.

The occurrence and distribution of calcitonin gene-related peptide (CGRP) immunoreactivity in the rat respiratory tract were investigated by means of immunocytochemistry and radioimmunoassay using antibodies raised in rabbits to synthetic rat CGRP. Substantial amounts of CGRP immunoreactivity (range 5-37 pmol/g) were detected in all parts of the respiratory tract, the highest being in the stem bronchus. Gel filtration chromatography of extractable CGRP immunoreactivity revealed one single peak, eluting at the position of synthetic rat CGRP. CGRP immunoreactivity was localized both in mucosal endocrine cells and nerve fibres from the larynx down to the peripheral lung. CGRP-immunoreactive endocrine cells were found singly in trachea and stem bronchi and in groups in intrapulmonary airways. They appeared at a late stage of gestation (17 days), reached a maximum number near term and decreased after birth to maintain a population similar to that of the adult animals by postnatal day 21. Similarly, CGRP-immunoreactive nerve fibres were first identified by day 18 of the gestation period and reached the adult distribution by postnatal day 21. CGRP-immunoreactive nerve fibres were localized among smooth muscle, seromucous glands, beneath and within the epithelium of the airways and around blood vessels. CGRP was also found in sensory ganglia and in motor end plates of the larynx musculature. Neonatal pretreatment with capsaicin caused a marked reduction in CGRP immunoreactivity of nerve fibres in the respiratory tracts as well as a less marked decrease in the population of CGRP-containing endocrine cells of the lung. No change was seen in motor end plates immunostaining. Vagal ligation experiments revealed that CGRP-immunoreactive nerve fibres travelling in the vagus originate mainly from neurons located in the jugular ganglion. Infranodosal right vagal ligation induced a marked loss in CGRP-immunoreactive nerves of the trachea, and of the ipsilateral stem bronchus, but no changes were observed in peripheral lung. By contrast infranodosal left side vagal ligation caused a decrease in CGRP-immunoreactive nerves of the ipsilateral lung and bronchus without affecting the peptide content in the trachea. Left vagal ligation also induced a marked increase in both the intensity of staining and number of CGRP-immunoreactive endocrine cells in the lung. We conclude that CGRP immunoreactivity is localized in both nerve fibres and endocrine cells and is associated principally with the afferent (sensory) innervation of the respiratory tract.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1986

Neuropeptides and dopamine in the marmoset. Effect of treatment with 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP): an animal model for Parkinson's disease?

Neurochemical studies of post-mortem human parkinsonian brains have demonstrated specific alterations in neuropeptide concentrations within the substantia nigra and striatal structures. The drug, 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP) has been reported to act as a selective toxin to nigrostriatal dopamine neurons, and induces a parkinsonian-like syndrome in primates. In this study, marmosets developed features typical of Parkinson's disease following treatment with MPTP for four days. The effects of MPTP treatment on the concentrations of dopamine and neuropeptides were determined and changes compared with those reported for Parkinson's disease. It was found that within the substantia nigra, substance P concentrations doubled following treatment with MPTP; in contrast, concentrations of vasoactive intestinal peptide and neuropeptide Y were significantly reduced. No changes were observed in the concentrations of six other neuropeptides measured in this region, notably cholecystokinin. Despite marked depletion of dopamine within the caudate nucleus and putamen, concentrations of all neuropeptides within these structures remained unchanged with the exception of an isolated reduction of neuropeptide Y within the putamen. Somatostatin concentrations within the frontal cortex and hippocampus were significantly elevated in the marmosets treated with MPTP. These neuropeptide changes in the CNS contrast with those reported for Parkinson's disease. In view of the autonomic dysfunction associated with Parkinson's disease, peripheral concentrations of neuropeptides were determined. Significant depletion of neuropeptide Y was identified in the ureter, adrenal and cardiovascular tissue. Thus the neurochemical changes induced by MPTP may not be as selective as previously reported.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1986

Long-term effects of intestinal alpha-glucosidase inhibition on postprandial glucose, pancreatic and gut hormone responses and fasting serum lipids in diabetics on sulphonylureas.

Seventeen non-insulin-dependent diabetics poorly controlled by diet and sulphonylurea drugs took part in a long-term (20-52 weeks) trial of the effect of an alpha-glucosidase inhibitor (acarbose 100 mg thrice daily) on postprandial glycaemic and gastro-entero-pancreatic hormone responses. Patients were assessed before, during, and after the trial period with identical 2.2 MJ mixed test meals plus placebo or acarbose 100 mg, and sulphonylurea therapy was continued throughout. Acarbose administration reduced the integrated postprandial plasma responses of glucose to 58 +/- 10% (mean +/- SEM, p less than 0.001), insulin to 61 +/- 10% (p less than 0.01) and gastric inhibitory polypeptide to 45 +/- 8% (p less than 0.001) of control values, increased the enteroglucagon response to 152 +/- 26% (p less than 0.001) of control and slightly prolonged the postprandial release of motilin. Recorded glycosuria was significantly (p less than 0.01) reduced throughout the treatment period. The effects of acarbose on postprandial glycaemic and endocrine responses remained approximately constant throughout the trial period, and responses returned to pre-treatment values within 2 days of stopping treatment.

Acarbose↗

PubMed1986

Effects of decapeptide of mammalian bombesin and neuromedin B on pancreatic exocrine secretion in the rat.

The effects on pancreatic exocrine secretion of intravenous bolus injections of decapeptide of mammalian bombesin (also called neuromedin C) and neuromedin B, recently isolated mammalian bombesin-like peptides, have been studied and compared with those of amphibian bombesin in anaesthetized rats. Decapeptide of mammalian bombesin and neuromedin B stimulated the volume output from the pancreas with the same potency as that with which they stimulated protein output, as did amphibian bombesin. The maximal peak rates of volume and protein secretion observed in the 5- to 10-min period after the injection of 3 X 10(-10) mol/kg decapeptide of mammalian bombesin were 24.5 +/- 1.2 microliters/5 min and 8.5 +/- 0.5 mg bovine serum albumin equivalents per 5 min (mean +/- SEM, n = 5). These rates were equivalent to those produced by the same dose of amphibian bombesin, but the duration of responses to decapeptide of mammalian bombesin were shorter than those of equimolar doses of amphibian bombesin. The relative potencies of decapeptide of mammalian bombesin and neuromedin B, calculated from the doses producing 50% of maximum effect on total responses, were, respectively, 100 and 0.5% of that of amphibian bombesin. The results suggest that decapeptide of mammalian bombesin, and possibly neuromedin B, could play a regulatory role in the control of exocrine pancreatic secretion.

Animals↗

PubMed1986

Production of pituitary protein 7B2 immunoreactivity by endocrine tumors and its possible diagnostic value.

7B2 is a protein originally isolated from pituitary, which has been shown to be present in the central nervous system and in certain peripheral tissues, with very high concentrations in pancreatic islets. Endocrine and nonendocrine tumors from 185 patients were investigated by RIA for the presence of immunoreactive pituitary protein 7B2. The highest mean concentration of 7B2 immunoreactivity was found in insulinomas [452 +/- 174 (+/- SEM) pmol/g wet wt tissue; n = 16], which was significantly higher than the concentration in normal adult pancreatic tissue (28.3 +/- 4.4 pmol/g; n = 7). High concentrations of 7B2 immunoreactivity also were found in other endocrine tumors. The cellular localization of 7B2 was studied in normal pancreas, pancreas with hyperplastic islets, and endocrine tumors. 7B2 immunoreactivity was localized to B-cells in the normal pancreas and to variable proportions of cells in islet cell hyperplasias, B-cell tumors, and pheochromocytomas. Plasma concentrations of 7B2 immunoreactivity also were determined in 255 patients with established diagnoses of endocrine or nonendocrine tumors. The proportion of patients with elevated plasma concentrations (arbitrarily set at more than 4 SD above the mean) were 42 of 72 with pancreatic islet cell tumors, 7 of 11 with midgut carcinoid tumors, and 5 of 13 with medullary carcinomas of the thyroid. Especially high values were found in patients with glucagonomas (14 of 20), vipomas (12 of 13), and pancreatic polypeptide-producing tumors (5 of 6). Thus, 7B2 immunoreactivity is produced by a variety of different tumors and may serve as a tumor marker, especially in patients with certain pancreatic islet tumors.

Adult↗

PubMed1985

Distribution and chromatographic characterization of neuromedin B-like immunoreactivity in the human spinal cord.

The quantitative regional distribution of neuromedin B-like immunoreactivity in normal postmortem human spinal cord was studied by a specific radioimmunoassay. Neuromedin B-like immunoreactivity was found in highest concentration in the dorsal part of the sacral cord. Chromatographic analyses by gel permeation and reverse-phase high-pressure liquid chromatography revealed two major peaks of neuromedin B-like immunoreactivity and the prevalent molecular form, approx. 90% of the total immunoreactivity, was chromatographically identical to synthetic porcine neuromedin B.

Aged↗

PubMed1985

Distribution and origin of calcitonin gene-related peptide (CGRP) immunoreactivity in the sensory innervation of the mammalian eye.

The occurrence, distribution, and origin of immunoreactive calcitonin gene-related peptide (CGRP) in nerves of rat, guinea pig, cat, and monkey eyes were investigated by immunocytochemistry, radioimmunoassay, and chromatography. A rich network of CGRP-immunoreactive nerve fibres was noted in the anterior uvea, which was widely distributed in both dilator and constrictor pupillae muscles and extended to the ciliary body and uveal blood vessels. Numerous CGRP-immunoreactive neuronal cells were present in the trigeminal ganglion. The extractable CGRP was 8.6 +/- 1.8 pmoles/gm of tissue in the iris and 44.0 +/- 8.1 pmoles/gm in the trigeminal ganglion. Following damage to the Gasserian ganglion a marked decrease of CGRP immunoreactivity was observed in the anterior uvea (control 11.3 +/- 1.6 pmoles/gm; operated 1.4 +/- 0.1 pmoles/gm) confirming the origin of the immunoreactive fibres from trigeminal primary sensory neurons. The sensory nature of the CGRP-immunoreactive fibres was substantiated by the depletion of CGRP immunoreactivity observed after treatment with capsaicin, which is known to cause selective degeneration of sensory neurons. Comparative studies on the distribution and colocalisation of CGRP and the putative sensory neurotransmitter substance P revealed a closely parallel distribution of the two peptides in certain regions of the uvea and their coexistence in a subpopulation of trigeminal primary sensory neurons. This study suggests that the sensory nervous system in the eye is more heterogeneous in terms of its putative neurotransmitters than previously indicated.

Animals↗

PubMed1985

Regulation of neuroendocrine gene expression by alternative RNA processing. Colocalization of calcitonin and calcitonin gene-related peptide in thyroid C-cells.

The generation of two discrete mRNAs encoding different polypeptide products in expression of the rat calcitonin, CGRP gene provides an example of developmentally determined alternative RNA processing events in the neuroendocrine system. Both mature mRNA transcripts and their peptide products, encoding either calcitonin or calcitonin gene-related peptide (CGRP) are co-produced in identical thyroid C-cells, in a ratio of 95:1, respectively. These data suggest that the generation of the two mRNAs reflect the actions of a factor(s) dictating alternative RNA processing events.

Animals↗

PubMed1985

Bombesin-like immunoreactivity in female rat genito-urinary tract.

The quantitative distribution and localization of bombesin-like immunoreactivity (BLI), by antiserum which cross-reacted fully with gastrin-releasing peptide (GRP), was determined by radioimmunoassay and immunocytochemistry in various regions of female rat urogenital tract. The highest concentration of BLI was found in the vagina, with lower but significant concentrations in the uterus and bladder. Bombesin-like immunoreactive nerve fibres were localized by immunocytochemistry in the smooth muscle layer, around blood vessels and in the submucosa of the vagina and bladder. BLI was separable into two immunoreactive peaks on both gel permeation chromatography and reverse phase HPLC. The major peak emerged exactly in the position of neuromedin C (C-terminal decapeptide of GRP) in both chromatographic systems, while the remaining immunoreactivity emerged close to the position of porcine GRP on gel permeation chromatography, but was easily distinguishable from this on HPLC. This suggests a significant species difference between rat and porcine GRP. Amphibian bombesin and mammalian neuromedin C have previously been shown to have potent biological actions in the rat urogenital tract. The presence of mammalian bombesin-like peptides in nerve fibres of the urogenital tract suggests that they may have a regulatory role in these organs.

Animals↗

PubMed1985

Neuropeptides in neurological tumours.

Concentrations of seven neuropeptides have been determined in 69 human neurological tumours. The majority of tumours were intrinsic to the central nervous system, being astrocytomas. In general, within the the better differentiated tumours (Grade I/II astrocytomas) higher concentrations of five neuropeptides (neuropeptide Y, somatostatin, substance P, vasoactive intestinal peptide and cholecystokinin) were measured in comparison to the poorly differentiated tumours. Of the metastatic tumours, five were derived from oat cell carcinoma of the bronchus. Very high concentrations of bombesin were identified in these metastases.

Astrocytoma↗

PubMed1985

Calcitonin gene-related peptide (CGRP)-immunoreactive sensory and motor nerves of the mammalian palate.

The distribution of calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibres in the palate of rat, cat and monkey was studied using immunocytochemistry and radioimmunoassay. CGRP-containing nerve fibres were found, in all species studied, to form a rich plexus in the subepithelial and submucous layers, around excretory ducts and blood vessels. A small number of CGRP-containing nerve fibres penetrated the epithelium of the hard and soft palate, and terminated as free endings. Some CGRP-containing nerve fibres were found in the vicinity of the mucous glands. CGRP-immunoreactive motor end plates were seen in the striated muscle (tensor veli palatini) of the soft palate. Following capsaicin treatment a small depletion in CGRP-immunoreactive nerve fibres in the rat palate epithelium was noted. In contrast, CGRP immunoreactive fibres forming rich plexuses in other layers of the palate, including motor end plates, were not affected. The extractable CGRP showed no significant depletion (normal animals [n = 10] 21.7 +/- 2.4 pmol/g compared with capsaicin-treated animals [n = 10] 17.5 +/- 1.8 pmol CGRP/g wet weight). The reduction in the number of visible immunoreactive nerves following capsaicin application tends to confirm the sensory character of the CGRP-containing nerve fibres terminating in the epithelium of the hard and soft palate. The capsaicin insensitive CGRP-immunoreactive nerve fibres may thus have a predominantly motor function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Calcitonin gene-related peptide immunoreactive sensory and motor nerves of the rat, cat, and monkey esophagus.

In the mammalian esophagus calcitonin gene-related peptide (CGRP)-immunoreactive nerves form abundant subepithelial plexuses and penetrate the mucosa. The levels of extractable CGRP in separated epithelial layers are 15.8 +/- 2.4 pmol/g wet wt of tissue (n = 8, mean +/- SEM). Treatment of neonatal rats with capsaicin and ablation of the central portion of the feline nodose ganglion led to a marked reduction in the numbers of CGRP-immunoreactive nerve fibers. The loss of CGRP nerves demonstrated by immunocytochemistry was accompanied by a parallel reduction in the tissue content of CGRP, as measured by radioimmunoassay (1.5 +/- 0.5 pmol/g in capsaicin-treated animals compared with 9.4 +/- 1.9 pmol/g in vehicle-treated controls; p less than 0.0025). These findings indicate the sensory nature of the CGRP-immunoreactive nerves. Substance P-immunoreactive nerve fibers innervated in particular the blood vessels of the lamina propria; very few penetrated the esophageal epithelium and these were only partially depleted after removal of the central portion of the nodose ganglion. The esophageal muscle contained nerves immunoreactive for substance P and, in particular, for CGRP which was also found in the motor end plates of the striated muscle. No changes in the CGRP-containing motor end plates were observed either after treatment of neonatal rats with capsaicin or ablation of cell bodies from the central portion of the nodose ganglion. These nerve fibers may originate from rostral areas of the nucleus ambiguus, where CGRP-immunoreactive motor neurons have previously been described. Thus, our findings reveal dual components, motor and sensory, of the CGRP-containing innervation of the esophagus.

Animals↗