Biomedical subjects

J M Allen

Publications and source records attributed to J M Allen.

At least 181 records · Page 10Linked to original sources

PubMed1986

Studies on cardiac distribution and function of neuropeptide Y.

High concentrations of a novel peptide, neuropeptide Y, have been demonstrated in the guinea-pig and canine heart and in the latter, a particularly high concentration was found in the region of the coronary vasculature (126 +/- 31 pmol g-1). Intra-arterial infusion of neuropeptide Y for 30 s into the coronary artery of the intact, innervated dog heart resulted in a rapid and short-lasting reduction of blood flow from 38 +/- 4 to 31 +/- 3 ml min-1 (P less than 0.05) to resume control level, 39 +/- 5 ml min-1, within 5 min. These injections were unaccompanied by changes in heart rate and aortic pressure, while there was an associated small reduction in dP/dt, used as a measure for changes in contractility. In vitro studies using the isolated, paced papillary muscle from cat, guinea-pig and rat, and spontaneously beating right atria from the guinea-pig, demonstrated no effect of NPY on active tension or beating frequency. The results indicate that NPY has vasoconstrictor properties, but under the test circumstances to lack both positive and negative inotropic and chronotropic effects.

Animals↗

PubMed1986

Beta-adrenergic inhibition of bovine mesenteric lymphatics.

The beta-action of catecholamines on lymphatic smooth muscle was studied by observing the effect of isoprenaline on electrical and mechanical activity in the double sucrose-gap. Action potentials and phasic contractions evoked by depolarizing pulses were abolished within 2 min of drug addition. Isoprenaline hyperpolarized the membrane and increased membrane conductance. Tetraethylammonium (10 mM) did not itself affect membrane resistance but reduced the hyperpolarization and the increase in conductance caused by isoprenaline. Removal of K+ from the external solution reduced membrane conductance and increased the hyperpolarization due to isoprenaline. When the NaCl content of Krebs solution was replaced with LiCl or choline chloride, isoprenaline no longer blocked action potential firing and its effects on phasic contractions and membrane conductance were reduced. In contrast, ouabain (10(-5) M) did not block the effect of isoprenaline on membrane potential and membrane conductance. These results suggest that beta-adrenergic inhibition of lymphatic smooth muscle involves an increase in an outward K+ current, though an additional metabolic effect cannot be ruled out.

Action Potentials↗

PubMed1986

Gastric regulatory peptides in rats with reduced acid secretion.

Gastric acid secretion is known to be controlled by a complex system of interacting factors. Amongst these, regulatory peptides make a significant contribution. In the present study, immunocytochemistry and radioimmunoassay were used to investigate gastric regulatory peptides in animals with pharmacologically reduced gastric acid secretion. Increased numbers of densely immunostained antral gastrin-immunoreactive (G) cells were seen in rats which had been rendered virtually achlorhydric by administration of high-dose (400 mumol/kg daily) omeprazole over a 10-week period. These morphological changes were accompanied by increases in the plasma, antral and fundic concentrations of gastrin, as measured by radioimmunoassay. In contrast, antral somatostatin-containing cells were reduced, and there was a corresponding fall in the tissue content of the peptide. Ten weeks after treatment had ceased, the peptide profiles had returned to normal. No other regulatory peptide, whether endocrine or neural, appeared to alter during treatment with high-dose omeprazole. Treatment with high-dose (700 mumol/kg daily) ranitidine also caused an elevation in the G cell population and the antral and plasma content of gastrin, but to a lesser extent than that observed during omeprazole treatment. Somatostatin cells and tissue levels did not alter in these animals, and no other morphological changes could be detected. Radioimmunoassay, however, measured reduced quantities of vasoactive intestinal peptide, peptide histidine isoleucine and calcitonin gene-related peptide. Achlorhydria, induced by omeprazole at a dosage of 250-500 times that required for effective acid inhibition in man and animals, therefore resulted in reciprocal changes in gastrin and somatostatin cells. These changes are support for the postulated roles of these peptides in the control of gastric acid secretion.

Achlorhydria↗

PubMed1985

Occurrence, distribution and nature of neuropeptide Y in the rat pancreas.

Significant quantities of a newly discovered peptide, neuropeptide Y, were found in the rat pancreas, where they were localized to nerves in the exocrine parenchyma and around arterial and ductal structures. Although unaffected by surgical parasympathectomy, the periarterial and periductal nerves were abolished by chemical sympathectomy, suggesting that NPY is partially costored with sympathetic transmitters in nerve fibers.

Animals↗

PubMed1985

The effect of sympathectomy on calcitonin gene-related peptide levels in the rat trigeminovascular system.

The effect of sympathectomy on the calcitonin gene-related peptide (CGRP) level in the rat primary trigeminal sensory neurone was investigated. Six weeks after bilateral removal of the superior cervical ganglion there was a 70% rise in the CGRP content of the iris and the pial arteries, a 34% rise in the concentration in the trigeminal ganglion but no change in the brainstem. The CGRP rise in both end organs suggests that this phenomenon may be common to all peripheral organs receiving combined sensory and sympathetic innervations. The lack of any rise in the brainstem CGRP content raises the possibility that this process spares central terminations. In contrast, the level of neuropeptide Y, a peptide mainly contained in sympathetic terminals, fell to 35% of control values in the iris and pial arteries whilst the trigeminal ganglion and brainstem concentrations remained unchanged. The possible relevance of these observations to the clinical syndrome of postsympathectomy pain (sympathalgia) is discussed. There are similarities between the delayed onset of the human pain state and the delayed rise in sensory peptides after sympathectomy.

Animals↗

PubMed1985

Dissociation of neuropeptide Y and somatostatin in Parkinson's disease.

The concentration of neuropeptide Y has been determined in the cortex and hippocampus of subjects with Parkinson's disease and compared to changes of activity of dopamine beta-hydroxylase and concentration of somatostatin. Despite a marked reduction in the concentration of somatostatin in the severely demented subject, in both cortex and hippocampus, no significant change in concentration of NPY was found in either region. This finding therefore suggests that the majority of NPY within the cortex is independent of somatostatin. This study provides some further evidence of neurochemical similarities between the dementia of Parkinson's disease and Alzheimer's disease.

Brain Chemistry↗

PubMed1985

Neuropeptide Y innervation of the rodent pineal gland and cerebral blood vessels.

Neuropeptide Y (NPY)-immunoreactivity has been shown to be present in sympathetic nerve fibres in the rat pineal gland and a dense network of NPY-containing nerve fibres demonstrated to innervate the rat circle of Willis. The NPY content of the major rabbit intracranial arteries was determined by radioimmunoassay and maximal levels found in the anterior cerebral arteries. After bilateral superior cervical ganglion (SCG) removal, no NPY was detectable in the rat pineal gland; however, significant NPY-immunoreactive nerve fibres remained throughout the rat vertebrobasilar arteries, and 47% of the assayable NPY was still present. Neither intraventricular 6-hydroxydopamine (6-OHDA) nor the combination of 6-OHDA treatment and SCG removal resulted in any further loss of NPY. In conclusion, the NPY innervation of the pineal gland originates exclusively from the peripheral sympathetic nervous system. In contrast the caudal portion of the rat circle of Willis contains NPY fibres which are resistant to sympathectomy.

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

Isolation and characterization of neuropeptide Y from porcine intestine.

The isolation and primary structure of intestinal neuropeptide Y (NPY) is described. The peptide was purified from porcine intestinal extracts using a chemical assay and radioimmunoassay for NPY. The amino acid sequence of this peptide is: Tyr-Pro-Ser-Lys-Pro-Asp-Asn-Pro-Gly-Glu-Asp-Ala-Pro-Ala-Glu-Asp-Leu-Ala- Arg-Tyr-Tyr- Ser-Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu-Ile-Thr-Arg-Gln-Arg-Tyr-NH2. This the structure of intestinal NPY is identical to the NPY of brain origin.

Amino Acid Sequence↗

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

Neuropeptide Y (NPY)-like immunoreactive amacrine cells in retinas of frog and goldfish.

The distribution of neuropeptide Y (NPY)-like immunoreactivity in rat, rabbit, chick, frog and goldfish retinas was investigated by immunohistochemistry. Positive results were observed only in the frog and goldfish retinas. NPY immunoreactivity was associated with a small population of amacrine cell bodies in the inner nuclear layer and cell processes in the inner plexiform layer of both retinas. In the frog retina, three distinct layers containing immunoreactivity were observed in the inner plexiform layer. In contrast, the immunoreactivity in the same area of the goldfish retina was more or less separated into two layers. Convincing evidence could not be found for the co-existence of NPY-like material with other putative transmitter-like substances in the two retinas. Radioimmunoassay revealed the presence of small amounts of NPY-like immunoreactivity in the rabbit retina; the goldfish and frog retinas contained significantly more immunoreactive material. High performance liquid chromatography of the immunoreactive material in frog and goldfish retinas showed each retina containing different molecular forms of NPY-like proteins, neither of which resembled porcine NPY or PYY. The endogenous NPY-like material of the frog retina can be released by potassium depolarisation in a calcium-dependent way. In view of all these data an NPY-like protein must now be considered a potential retinal transmitter.

Animals↗

PubMed1985

Quantitation and characterization of human plasma neurotensin-like immunoreactivity in response to a meal.

The secretion and metabolism of endogeneous neurotensin-like immunoreactivities after a test meal were studied in five healthy human subjects. Intact neurotensin and the N-terminal metabolic fragment, neurotensin 1-8, were quantified by radioimmunoassay with C- and N-terminally directed antisera in conjunction with gel filtration of plasma samples obtained at timed intervals. Both C- and N-terminal neurotensin-like immunoreactivities rose after the meal, reaching a plateau level after 20 and 30 min, respectively. During the plateau phase, which lasted for the rest of the experimental period of 180 min, the molar ratio of intact neurotensin to neurotensin 1-8 remained approximately constant at 1:4.6. Meal-stimulated immunoreactive neurotensin appeared to be metabolized in a manner comparable to that of exogenously infused neurotensin in man. The results suggest that intact neurotensin is secreted at an approximately constant rate during the plateau phase. The relatively low plateau level of neurotensin 1-8, which has a much longer half-life than intact neurotensin in the circulation, implies that only a fraction of the secreted intact neurotensin is metabolized to neurotensin 1-8, indicating the existence of alternative pathways of neurotensin metabolism.

Adolescent↗

PubMed1985

Effect of peptide YY on gastric, pancreatic, and biliary function in humans.

The effect of peptide YY (PYY) on gastric and pancreatico-biliary secretion was studied in humans. Peptide YY was infused into groups of 6 healthy volunteers at doses of 0.59, 0.20, and 0.064 pmol X kg-1 X min-1. The two higher doses caused a significant suppression of gastric acid and pepsin output during background stimulation with pentagastrin. The middle dose of PYY (0.20 pmol X kg-1 X min-1) that increased plasma PYY levels by 27 +/- 2 pM caused a 90% +/- 18% (mean +/- SEM; p less than 0.001) reduction in the incremental gastric volume response to pentagastrin. Similarly this dose of PYY caused a substantial inhibition of the acid (77% +/- 14%; p less than 0.005) and pepsin (96% +/- 22%; p less than 0.01) response to pentagastrin; in 2 subjects, pepsin output fell to below basal levels. In contrast, the highest dose of PYY (0.62 pmol X kg-1 X min-1) had no significant influence on duodenal juice volume, output of bicarbonate, trypsin, or bilirubin during low dose stimulation with secretin (0.25 pmol X kg-1 X min-1) and cholecystokinin-8 (0.15 pmol X kg-1 X min-1). Thus PYY concentrations in the circulation similar to those seen after the ingestion of food cause a marked reduction in gastric secretion. This peptide should therefore be considered as one of the possible candidates for the classical enterogastrone.

Adolescent↗

PubMed1985

Presence of the predicted C-flanking peptide of neuropeptide Y (CPON) in tissue extracts.

Isolation of the DNA sequence encoding neuropeptide Y (NPY) has suggested the presence of a precursor peptide consisting of 97 aminoacids. Three peptide products have been predicted from this precursor; an N terminal signal peptide, neuropeptide Y and a C terminal 30 amino acid flanking peptide. This study has demonstrated by a novel radioimmunoassay that this C-flanking peptide for NPY occurs naturally in tissues. The peptide is present in abundance throughout the central nervous system and qualitatively in both the brain and peripheral structures, it has the same distribution as NPY. Chromatographic analysis demonstrated that the measured CPON-immunoreactivity elutes in the position of the peptide synthesised according to the predicted sequence.

Adrenal Glands↗

PubMed1985

Immunohistochemical analysis of the early ontogeny of the neuropeptide Y system in rat brain.

The distribution of neuropeptide Y in the developing rat brain was studied with immunocytochemistry, using the peroxidase-antiperoxidase method. Immunoreactive perikarya were first seen on embryonic day 13 and staining of fibres appeared from embryonic day 15 onwards: perikaryal staining was generally more intense prenatally than after birth. Areas rich in neuropeptide Y immunostaining included the monoaminergic regions of the brain stem from embryonic day 13 (especially the lateral reticular nucleus and the medullary reticular formation), the dorsal mesencephalon (with spots of immunoreactivity in the outer subventricular zone at embryonic days 13 or 14 and many cells and fibres in the inferior colliculus from embryonic days 16-20) and the olfactory tubercle/ventral striatum from embryonic day 15 until birth. The period of development of cortical neurones extended from embryonic day 19 until postnatal day 21. A hitherto unreported feature unique to neuropeptide Y was the presence in certain parts of the cerebral cortex of transient cells at the base of the cortical plate bearing radial processes which transverse its width. They were present from embryonic day 17 until postnatal day 4 and were maximally developed at embryonic days 20 or 21, contributing at this age a substantial fibre projection through the immature corpus callosum. The abundance of neuropeptide Y in the prenatal rat brain suggests it may play an important role in development.

Age Factors↗

PubMed1985

Calcitonin gene-related peptide in cardiovascular tissues of the rat.

The distribution of calcitonin gene-related peptide immunoreactivity in the cardiovascular system of the rat was investigated by radioimmunoassay and immunocytochemistry. The nature of the immunoreactivity was studied by gel permeation and high performance liquid chromatography. Immunocytochemistry demonstrated the existence of calcitonin gene-related peptide-containing nerve fibres throughout the cardiovascular system. These were present in all regions of the heart, particularly in association with the coronary arteries, within the papillary muscles and within the sinoatrial and atrioventricular nodes. Calcitonin gene-related peptide-containing fibres were found mainly in the adventitia of the arteries and veins. Calcitonin gene-related peptide concentrations were high in major arteries and veins but comparatively low in the heart, aortic arch and thoracic aorta. Chromatography showed that approximately 70% of the total immunoreactivity was identical to synthetic calcitonin gene-related peptide. Calcitonin gene-related peptide concentrations in the blood vessels of rats treated neonatally with capsaicin were not found to be significantly different from those in control animals although capsaicin caused significant reductions of calcitonin gene-related peptide levels in certain other tissues. The results of this study suggest that calcitonin gene-related peptide-containing fibres are likely to be of importance in the innervation of vascular tissues and raise the possibility that these fibres are different in character from calcitonin gene-related peptide-containing fibres found in other tissues.

Animals↗

PubMed1985

Neuropeptides in the brain.

In recent years, there has been a remarkable increase in the identification of neuropeptides. These peptides have become known as neuropeptides, as they have been identified within neuronal structures and frequently localised to nerve terminals. Classification of newly discovered peptides is attempted according to function or structure. Although the role of the hypothalamic releasing factors is readily appreciated, the functional significance of the remaining neuropeptides is often not easily determined. However, these peptide appear to interact with conventional transmitters and may be implicated in neuropathology.

Alzheimer Disease↗

PubMed1985

Neuropeptide Y: a novel renal peptide with vasoconstrictor and natriuretic activity.

A novel vasoconstrictor peptide, neuropeptide Y (NPY), has been identified in considerable quantities in the renal artery and kidney. Within the kidney, NPY was confined to the cortex and corticomedullary interface, the regions where the juxtaglomerular apparatus is most numerous. In the isolated perfused rat kidney, NPY caused a prompt dose-dependent increase in perfusion pressure and reduction in flow, with only a small fall in glomerular filtration rate (GFR). In spite of the reduced renal perfusion, a dose-dependent natriuresis was observed. This response contrasts to the response of this preparation to noradrenaline, which causes sodium reabsorption. The presence of a potent vasoconstrictor and natriuretic peptide within the rat renovascular system suggests that it may play a significant role in the control of renal function.

Animals↗