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Biomedical subjects

G J Dockray

Publications and source records attributed to G J Dockray.

At least 181 records · Page 10Linked to original sources
PubMed1982

Capsaicin depletes CCK-like immunoreactivity detected by immunohistochemistry, but not that measured by radioimmunoassay in rat dorsal spinal cord.

In rats treated neonatally with capsaicin there were significant reductions in substance P measured by radioimmunoassay in dorsal spinal cord, spinal ganglia, and coeliac ganglia, but concentrations of cholecystokinin octapeptide (CCK8) measured by radioimmunoassay were not decreased. However, immunohistochemical studies using antisera to both substance P and CCK8, respectively, demonstrated decreased immunoreactive material in the dorsal horn of the spinal cord. The nature of the material localized by CCK8 antiserum in immunohistochemistry remains to be resolved.

Animals↗
PubMed1982

FMRFamide-like immunoreactivity in the nervous system of Hydra.

FMRFamide-like immunoreactivity has been localized in different parts of the hydra nervous system. Immunoreactivity occurs in nerve perikarya and processes in the ectoderm of the lower peduncle region near the basal disk, in the ectoderm of the hypostome and in the ectoderm of the tentacles. The immunoreactive nerve perikarya in the lower peduncle region form ganglion-like structures. Radioimmunoassays of extracts of hydra gave displacement curves parallel to standard FMRFamide and values of at least 8 pmol/gram wet weight of FMRFamide-like immunoreactivity. The immunoreactive material eluted from Sephadex G-50 in several components emerging shortly before or after position of authentic FMRFamide. The presence of FMRFamide-like material in coelenterates shows that this family of peptides is of great antiquity.

Animals↗
PubMed1982

A rational approach to the fixation of peptidergic nerve cell bodies in the gut using parabenzoquinone.

Study of the possible chemical mechanisms by which parabenzoquinone acts as a fixative in the localisation of neuronal peptides by immunohistochemistry suggested several possible improvements to standard techniques. In particular, by using favourable conditions for regenerative oxidation reactions, i.e. fixing at 37 degrees C in well oxygenated, slightly alkaline buffer, it was possible to improve the localisation of substance P-, vasoactive intestinal polypeptide-, enkephalin- and somatostatin-like immunoreactive peptides such that nerve cell bodies were routinely visualised without the use of drugs to block axonal transport. Application of the improved fixation method is likely to facilitate study of the organisation of peptidergic systems.

Animals↗
PubMed1982

Identification and measurement of molecular variants of cholecystokinin in duodenal mucosa and plasma. Diminished concentrations in patients with celiac disease.

The amount and type of cholecystokinin (CCK) in duodenal extracts and plasma of celiac patients and normal subjects was studied by radioimmunoassay and gel filtration. In both groups there were similar patterns of molecular forms in extracts of duodenal biopsies, but concentrations in celiac disease were significantly depressed. In boiling water extracts of duodenal mucosa from both groups a factor with the properties of the COOH-terminal octapeptide of cholecystokinin predominated, but there were also significant amounts of a larger molecular weight form. In acid extracts of mucosa a factor with the properties of the 33 or 39 residue form was identified in amounts that were approximately 25% those of CCK8; there were also similar amounts of an acid-soluble form that had an apparent molecular weight higher than CCK39. Plasma immunoreactive cholecystokinin was studied after concentration by immunoaffinity adsorption and fractionation by gel filtration. In normal subjects fasting CCK-like immunoreactivity was less than 0.8 pmol/liter, and after a light breakfast increased to 2.0 +/- 0.7 (range 1.0 to 4.8) pmol/liter; CCK8-like activity accounted for all the increased immunoreactivity. In five of six celiac patients the concentrations of both fasting and postprandial CCK-like immunoreactivity in plasma were undetectable (less than 0.8 pmol/liter). We conclude that diminished production and release of CCK could account for the impaired pancreatic and gall bladder responses to intraluminal stimuli in celiac disease.

Adult↗
PubMed1982

Distribution and development of peptidergic nerves and gut endocrine cells in mice with congenital aganglionic colon, and their normal littermates.

Studies were made of the distribution of gut hormones and neuropeptides in the gastrointestinal tract of mice with hereditary aganglionic colon (s1/s1) and their normal littermates. Antisera to substance P, vasoactive intestinal polypeptide, and enkephalins demonstrated markedly diminished numbers of immunofluorescent nerve fibers in the aganglionic segment of colon; in contrast, in proximal colon and small intestine the distribution of peptidergic nerve fibers was essentially normal. Mucosal endocrine cells were demonstrated in the colon by antisera to substance P, somatostatin, glucagon, and cholecystokinin; in each case there were similar numbers of cells in s1/s1 and normal mice. Radioimmunoassays for vasoactive intestinal polypeptide and bombesin showed diminished concentrations of immunoreactive material in the aganglionic segment of colon of 16-17-day-old animals. However, assays for CCK--which is predominantly located in endocrine cells--showed similar concentrations of immunoreactive material throughout the gut of s1/s1 and normal mice. It was of interest that the concentrations of immunoreactive substance P were lower than normal not only in the aganglionic segment of colon, but also in proximal colon and distal small intestine, and that at all ages the development of substance P in the intestine was delayed in the s1/s1 mice. The results are consistent with the idea that the constriction of the aganglionic segment of colon develops as a consequence of lack of intrinsic inhibitory neurons, possibly those containing vasoactive intestinal polypeptide. The presence of an aganglionic segment is attributable to delayed migration of the neuroblasts from the neural crest. Thus the findings of normal populations of gut endocrine cells in the aganglionic segment is further support for the view that the embryologic origin of gut endocrine cells is different to that of gut neurons.

Animals↗
PubMed1982

Identification of NH2-terminal fragments of big gastrin in plasma.

Molecular forms of gastrin in human plasma were studied by radioimmunoassay using antisera specific for the NH2-terminus of big gastrin (gastrin 34). A plasma enzyme system that destroys immunoreactivity of NH2-terminal fragments of gastrin 34, but not of gastrin 34 itself, has been demonstrated and shown to be inhibited by phenanthroline. Endogenous immunoreactive human plasma gastrin that had been concentrated by immunoaffinity adsorption and separated by gel filtration was shown to consist of gastrin 34, together with peptides corresponding to its NH2-terminal tryptic peptide and a shorter NH2-terminal fragment. The latter material does not occur in antral extracts and cannot be generated by in vitro incubation of plasma and antral extracts, suggesting that it is produced by passage through a capillary bed of gastrin 34 or its NH2-terminal tryptic peptide or both. The results are of significance in understanding the mechanisms of secretion and metabolism of different forms of gastrin.

Adult↗
PubMed1981

Evidence that the action of cholecystokinin octapeptide on the guinea pig ileum longitudinal muscle is mediated in part by substance P release from the myenteric plexus.

Studies were made on the mode of action of cholecystokinin octapeptide (CCK8) on longitudinal muscle strips of guinea pig ileum in vitro. CCK8 produced dose-related contractions of innervated strips of ileum longitudinal muscle (EC50 3--4 x 10(-9) M), but was inactive on denervated strips. Tetrodotoxin, and reducing the bath temperature to 15 degree C, abolished the response of innervated strips to CCK8. These results indicate that the action of CCK8 on ileal longitudinal muscle is mediated by the myenteric plexus. Atropine abolished the responses to acetylcholine and to low doses of CCK8. However, the responses to CCK8 in doses above 10(-8) M were reduced by atropine but not abolished. Incubation of longitudinal muscle strips with high concentrations of substance P (1.5 x 10(-7) M) resulted in desensitization to this peptide; this treatment inhibited the responses to CCK8 alone, and abolished the atropine-resistant actions of CCK8. Desensitization to substance P had no effect on the responses to acetylcholine, histamine, serotonin and angiotensin II. The results indicate that CCK8 contracts the longitudinal muscle of guinea pig ileum by releasing acetylcholine and substance P from the myenteric plexus.

Acetylcholine↗
PubMed1981

Bombesin-like immunoreactivity in the nervous system of hydra.

With immunocytochemical methods, nerve cells have been detected in Hydra attenuata containing bombesin-like immunoreactivity. These nerve cells are located in ectoderm of all body regions of the animal and are especially abundant in basal disk and tentacles. Radioimmunoassay of extracts of hydra demonstrated at least 0.2 pmol/g wet weight of bombesin-like immunoreactivity. The immunoreactive material elutes from Sephadex G-50 in a similar position to synthetic bombesin. The data show that bombesin-like peptides are among the phylogenetically oldest neuropeptides found so far.

Animals↗
PubMed1981

Neuropeptides in Alzheimer's disease, depression and schizophrenia. A post mortem analysis of vasoactive intestinal peptide and cholecystokinin in cerebral cortex.

Vasoactive intestinal peptide (VIP) and cholecystokinin (CCK) have been measured, by radioimmunoassay, in cerebral cortex obtained at autopsy from patients without neurological or psychiatric disease and from patients with Alzheimer's disease, depression and schizophrenia. Sephadex gel filtration indicated that over 90% of the CCK immunoreactivity was associated with the octapeptide in extracted material from the different clinical groups investigated. There were no significant differences from the normal in the overall concentrations of either VIP or CCK in any of the psychiatric groups examined, although differences in Alzheimer's disease were apparent when cases were grouped according to postmortem delay.

Alzheimer Disease↗
PubMed1981

Vertebrate brain-gut peptides related to FMRFamide and Met-enkephalin Arg6Phe7.

Many mammalian brain-gut peptides are known to be represented in invertebrate nervous systems; we have now examined the possibility that an invertebrate neuropeptide occurs in vertebrates. Antisera were raised in rabbits to the molluscan neuropeptide. Phe-Met-Arg-Phe-NH2 (FMRFamide). The antiserum used for radioimmunoassay and immunocytochemistry is highly specific for the C-terminus of the tetrapeptide. In radioimmunoassays of tissue extracts of brain, gut and pancreas of various vertebrates (chicken, frog, dog, rat) concentrations of immunoreactive material up to about 200 pmol/g have been recorded. The immunoreactive material in chicken pancreas behaves on gel filtration and ion exchange chromatography as a molecule that is larger and less basic peptide that FMRFamide. Immunocytochemical studies have demonstrated an endocrine cell origin for FMRFamide-like material in chicken pancreas, and in dog ileum. In brain, FMRFamide can be localised to nerve cell bodies (frog) and nerve fibres (frog and rat). Synthetic FMRFamide has been shown to have excitatory actions on brain stem neurons in the rat. It is suggested that neurons in the rat central nervous system have receptors for FMRFamide that normally bind endogenous material with FMRFamide immunoreactivity.

Animals↗
PubMed1981

Neurochemical activities in human temporal lobe related to aging and Alzheimer-type changes.

Activities relating to 3 neurotransmitter and 4 neuropeptide systems have been examined in human temporal lobe (post mortem) for their relationships with age and Alzheimer-type changes (senile plaques and cognitive function). Significant alterations with increasing age (from 61 to 92 years) in a series of non-demented cases included a reduction of the cholinergic enzyme, choline acetyltransferase, and an increase in vasoactive intestinal peptide immunoreactivity. In cases of alzheimer's disease the only neurochemical activity investigated which correlated significantly with cognitive impairment (assessed from a Mental Test Score obtained shortly before death) and with the severity of Alzheimer-type abnormalities (senile plaques density) was choline acetyltransferase. Further analyses of the data in relation to the severity of plaque formation suggest that alterations in other neurochemical activities including reductions in dopamine-beta-hydroxylase activity, cholecystokinin octapeptide (aqueous extracted) and somatostatin immunoreactivities and an increase in substance P immunoreactivity, may occur at later stages of the disease process. These comparative data suggest that biochemical changes in this brain area associated with age and earlier stages of Alzheimer's disease may be relatively selective.

Aged↗
PubMed1981

Localization of cholecystokinin immunoreactivity in amacrine cells of the retina.

The distribution of cholecystokinin-like immunoreactivity within frog retina was studied by immunofluorescence. Positive staining for cholecystokinin was observed in the somata of some amacrine cells and their processes within the inner plexiform layer. Chromatography of frog retinal extracts on Sephadex G-50 and parallel dilution curves show that the retinal cholecystokinin-like immunoreactivity was also found to be associated with human and bovine retinas but absent from other ocular tissue.

Animals↗