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Biomedical subjects

K A Sharkey

Publications and source records attributed to K A Sharkey.

106 records · Page 6Linked to original sources
PubMed1989

Effects of capsaicin in rat and pigeon on peripheral nerves containing substance P and calcitonin gene-related peptide.

Substance P and calcitonin gene-related peptide were immunohistochemically identified in axons innervating the cornea and the ureter of adult rats and pigeons. The two neuropeptides were similarly distributed in both species. Capsaicin pretreatment induced depletion of the immunoreactivity; this was quantitatively and qualitatively different in rats and pigeons. Topical application of capsaicin (1%) reduced the immunoreactivity in the cornea in both species by 50%. Systemic capsaicin treatment completely depleted both peptides from the corneal innervation of rats but reduced the peptide content only by 50% in the cornea of pigeons. In the ureter of rats, capsaicin pretreatment completely depleted the peptide immunoreactivity. In pigeons the peptide depletion was only complete in the outer longitudinal muscle layer. Whereas only a few immunoreactive fibres were observed in the circular muscle layer, about 50% of the peptide remained in the inner longitudinal muscle layer. The results demonstrate that peptidergic afferents in the cornea and ureter of pigeons are sensitive to capsaicin, although birds do not show nociceptive responses to local administration of the drug. The long-term depletion of substance P and calcitonin gene-related peptide by capsaicin is discussed with regard to the possibility that functionally capsaicin receptors may exist in the axon but not at nerve endings.

Animals↗
PubMed1989

The effects of streptozotocin-induced diabetes on the peptidergic innervation and function of the rat parotid gland.

The effects of streptozotocin-induced diabetes on the function and pattern of innervation of the rat parotid gland were investigated. An in vitro preparation was used to measure amylase release and immunohistochemistry was used to examine the innervation of the gland. Basal amylase release and the response to field stimulation were reduced in diabetic animals. In the presence of atropine or a propranolol/phentolamine mixture both control and diabetic responses were attenuated. When all 3 antagonists were present the response to field stimulation (non-adrenergic, non-cholinergic [NANC] response) was about 30% of maximal in untreated rats but virtually abolished in diabetic animals. Substance P (SP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) all stimulated amylase release in untreated rats. However, in diabetic rats the responses to all 3 peptides were reduced. No differences in staining were observed between control and diabetic rats with antisera to tyrosine hydroxylase, substance P. VIP or calcitonin gene-related peptide. In contrast there was a marked reduction in NPY-like immunoreactivity in the acinar tissue of diabetic rats. These data suggest that the diabetic rats had a failure of NANC transmission which appears to be due to a reduced NPY innervation and a lack of responsiveness to peptidergic (SP, VIP and NPY) agonists.

Amylases↗
PubMed1989

Visceral and somatic afferent origin of calcitonin gene-related peptide immunoreactivity in the lower thoracic spinal cord of the rat.

The origin of calcitonin gene-related peptide in the thoracic spinal cord of the rat was investigated by radioimmunoassay and immunohistochemistry. In transverse sections from normal animals there was a dense staining of calcitonin gene-related peptide-immunoreactivity in laminae I, II and V of the dorsal horn. In parasagittal sections this was found to consist of rostrocaudally orientated fibres in laminae I and II and longitudinal bundles of fibres interspersed with a plexus of immunoreactivity in lamina V. After sectioning the thoracic spinal nerves there was a significant reduction in immunoreactivity in the dorsal horn of the spinal cord which was seen as a marked reduction of staining in lamina II and in the bundles of fibres in lamina V. Section of the splanchnic nerve slightly reduced staining in lamina I and virtually abolished the plexuses of immunoreactivity in lamina V. However, measurement of calcitonin gene-related peptide in samples from coeliac-ganglionized rats revealed an increase in immunoreactivity in regions of the spinal cord containing lamina V. These results provide evidence of a visceral and somatic afferent origin of calcitonin gene-related peptide in the thoracic spinal cord of the rat.

Animals↗
PubMed1988

An electrophysiological and anatomical study of intestinal afferent fibres in the rat.

1. The afferent innervation of the distal ileum has been examined in normal rats and in rats treated at birth with capsaicin. Electrophysiological recordings were made using an in vitro preparation of distal ileum and its associated mesenteric nerves. The fibre composition of the mesenteric nerves was examined by electron microscopy and the numbers of primary afferent fibres innervating a segment of distal ileum was estimated using retrograde tracing. 2. Recordings were made from 120 single afferent units all of which showed some degree of background activity. The conduction velocities of sixty-seven afferent units were estimated, and all were found to be in the C-fibre range (less than 2 m/s). Eighty-two units were sufficiently studied to allow their classification according to whether they responded to mechanical stimuli (M units), chemical stimuli (Ch units) or both mechanical and chemical stimuli (MCh units). In control rats 85.5% were classified as MCh units, 11.9% as M units and 2.6% as Ch units. In capsaicin-treated rats six single and three multi-units were MCh and one multi-unit was classified as an M recording. 3. The effects of intraluminal distension were investigated in sixty-seven units which were classified according to whether or not they adapted during the distension. About half the total units were classified as rapidly adapting, the other half were slowly adapting. This distribution was similar for the MCh-units, but of the eight M units tested, seven adapted during distension. The distension thresholds were tested in thirty units, of which twenty-eight responded at thresholds below 18 mmHg. There were no differences in the thresholds of units from control and capsaicin-treated rats. 4. The chemosensitivity of units was tested in response to acetylcholine (ACh), bradykinin and substance P. Most units tested responded to ACh (78% of MCh units tested) and bradykinin (80% of MCh units), but fewer units responded to substance P (about 50% of MCh units). ACh produced an increased tension which outlasted the increase in afferent activity. Bradykinin gave long-lasting afferent responses which were not always accompanied by increases in tension. The increases in afferent activity produced by substance P were often seen after an increase in tension. 5. The fluorescent dye True Blue injected into the wall of the ileum labelled cell bodies in the spinal and nodose ganglia, predominantly on the left side of an animal. The mean number of labelled cells per animal was eighty-seven, of which the majority was in the T10-T13 spinal ganglia.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1987

Evidence for a visceral afferent origin of substance P-like immunoreactivity in lamina V of the rat thoracic spinal cord.

A visceral afferent origin of substance P-like immunoreactivity in lamina V of the lower thoracic spinal cord of the rat was investigated. In transverse sections from normal animals there was a moderately dense substance P-immunoreactive innervation of lamina V. In some sections there was a dorsoventrally orientated fibre bundle from the superficial dorsal horn entering lamina V. In parasagittal sections, substance P-immunoreactivity in lamina V was found arranged in clusters, with a periodicity in the rostrocaudal axis of 200-600 microns. In some cases these were seen to be continuous with a dorsoventrally orientated fibre bundle from the superficial dorsal horn. After section of the splanchnic nerve there was a consistent reduction in the density of the substance P-like immunoreactivity in lamina V, with fewer clusters on the operated side. Adult rats treated neonatally with capsaicin showed a substantial reduction of substance P-immunoreactivity in laminae I and II and the virtual abolition of staining in lamina V. These results provide evidence of a visceral origin for some of the substance P-like immunoreactivity in lamina V of the rat thoracic spinal cord. In addition, they confirm that most of the substance P-immunoreactivity in the dorsal horn is of primary afferent origin.

Animals↗
PubMed1987

The organization of capsaicin-sensitive visceral afferent systems.

It has become clear that a number of neuropeptides are found in sensory nerves, some of which have been identified in visceral afferents. The best studied peptide is substance P, which has been localized in a population of capsaicin-sensitive visceral afferents. It has been established that there are a varied proportion of substance P-containing afferents in different visceral structures. In general, the peripheral termination of these nerves is around blood vessels. The central terminations of visceral afferents are in laminae I and V in the dorsal horn of the spinal cord. Substance P has been localized in these laminae and appears to be capsaicin-sensitive and therefore of sensory origin. Recently, substance K, which is derived from the same gene as substance P, has been found in visceral structures. Calcitonin gene-related peptide has been found in certain viscera to be contained in capsaicin-sensitive nerves. The contribution that other peptides make to visceral afferent innervation is not known.

Abdomen↗
PubMed1986

Evidence for a role of capsaicin-sensitive mucosal afferent nerves in the regulation of mesenteric blood flow in the dog.

Capsaicin injected into the lumen of the small intestine produced marked changes in mesenteric blood flow in anesthetized dogs. In the majority of cases capsaicin evoked a significant increase in mesenteric blood flow, the time-course of which indicated it was of a reflex nature. The response to capsaicin was completely abolished by a previous intraluminal application of the local anesthetic lidocaine, and was inhibited by an intraarterial injection of somatostatin. The present findings suggest that the effects of capsaicin may be related to a release of vasoactive peptides from afferent nerves associated with the vascular system of the gastrointestinal tract. It is concluded that capsaicin-sensitive mucosal afferent nerves, possibly provided with an axon reflex arrangement, may play a role in the regulation of local intestinal blood flow.

Animals↗
PubMed1986

An in vitro method for recording single unit afferent activity from mesenteric nerves innervating isolated segments of rat ileum.

A technique has been developed for recording single unit afferent activity from mesenteric nerves in isolated segments of rat distal ileum in vitro. The preparation consists of a 3-cm segment of ileum, containing a single neurovascular bundle, held horizontally in an organ bath. One end of the segment is attached to a tension transducer to record changes in longitudinal tension of the gut muscle and the other is connected to a pressure transducer to record changes in intra-luminal pressure. Electromyographic activity of the smooth muscle is recorded using glass-insulated tungsten microelectrodes inserted in the wall of the gut. Afferent nerve activity is recorded with a monopolar platinum wire electrode from filaments of the mesenteric nerves that run between the artery and vein supplying the segment. This preparation permits the detailed analysis of the electrical activity of intestinal afferent nerve fibres correlated with mechanical and chemical events occurring naturally in the gut or imposed experimentally on it.

Animals↗
PubMed1985

Cholecystokinin and gastrin forms in the nervous system.

Cholecystokinin octapeptide is the predominant representative of the gastrin-CCK family in the central nervous system. Other forms occur in low concentrations, or restricted locations, as do the gastrins. The pathways of biosynthetic processing can now be studied in detail, following the elucidation of the cDNA sequence for the two peptides. In the vagus both CCK and gastrin can be found. Brain stem neurons receiving an input from gastric mechanoreceptors respond to CCK-8, but most do not respond to gastrin given intravenously or intra-arterially. This system, which may well be involved in mediating the peripheral satiety effect of CCK, is therefore able to distinguish between the two peptides.

Amino Acid Sequence↗
PubMed1984

Substance P in the rat parotid gland: evidence for a dual origin from the otic and trigeminal ganglia.

The substance P innervation of the rat parotid was investigated using retrograde tracing with the fluorescent dye True Blue, in combination with the immunohistochemical localization of substance P. Retrogradely-labelled cells were seen in the otic, trigeminal, superior cervical and nodose ganglia. A proportion of the True Blue-labelled cells in the otic and trigeminal ganglia also contained substance P-like immunoreactivity providing direct evidence for a dual origin of substance P in the rat parotid. In addition, these results imply that in the rat otic ganglion substance P and acetylcholine coexist.

Animals↗
PubMed1984

Sensory substance P innervation of the stomach and pancreas. Demonstration of capsaicin-sensitive sensory neurons in the rat by combined immunohistochemistry and retrograde tracing.

The sensory innervation of the stomach and pancreas has been identified by retrograde tracing using the fluorescent dye True Blue (Illing, Gross-Umstadt, Federal Republic of Germany), coupled with the immunohistochemical localization of substance P. Labeled cells were visualized in spinal ganglia, nodose ganglia, celiac ganglion, and dorsal motor nucleus of the vagus after injection of True Blue into both stomach and pancreas. Substance P immunoreactivity was found in 35%-50% of gastric spinal afferent neurons and in approximately 15% of pancreatic spinal afferents. In rats treated at birth with the sensory neurotoxin capsaicin there was a reduction of about 70% in True Blue-labeled cells in the spinal and nodose ganglia, and virtually complete loss of substance P in these ganglia. There was also a marked depletion of substance P-immunoreactive fibers in the pancreas, and in the submucosa of the stomach. The results suggest that the substance P-containing spinal afferents that project to the gastric submucosa are an important component of the gastric sensory innervation.

Animals↗
PubMed1983

Extrinsic innervation of the rat pancreas: demonstration of vagal sensory neurones in the rat by retrograde tracing.

The extrinsic innervation of the rat pancreas was examined using retrograde tracing with the fluorescent dye True Blue. Retrogradely-labelled cell bodies were seen bilaterally in the nodose ganglia, and in the spinal ganglia at levels T6-L2. Labelled cells were also seen in the dorsal motor nucleus of the vagus, the nucleus ambiguus and the coeliac ganglion. Our results provide new and direct evidence for a vagal sensory innervation of the pancreas.

Animals↗
PubMed1983

Sensory substance P-innervation of the urinary bladder: possible site of action of capsaicin in causing urine retention in rats.

In rats treated neonatally with capsaicin there is, in later life, a tendency tendency towards urine retention. Since capsaicin is known to cause irreversible loss of certain primary sensory neurons, notably those containing substance P, we have studied the sensory innervation of the bladder in capsaicin-treated and control rats using retrograde tracing methods and immunohistochemistry; in addition, the motor function of the bladder was assessed in in vitro experiments, using electrical field stimulation. Five days after injection of the fluorescent tracer True Blue into the wall of the bladder, numerous labelled cells were identified in dorsal root ganglia T13, L1, L2, L6, and S1 and smaller numbers of cells were found in T12 and L3. In capsaicin-treated rats the numbers of labelled cells were reduced by over 50% in L1, L6 and S1. In control rats, 10-16% of True Blue labelled cells also contained substance P as demonstrated by indirect immunofluorescence, but in capsaicin-treated rats substance P cells were virtually absent. In in vitro studies, contractions of the detrusor muscle to electrical field stimulation, both before and after atropine, were similar in control and capsaicin-treated rats. We suggest that capsaicin causes urine retention in rats due to an impairment of sensory transmission from the bladder (that could involve substance P) and a consequent failure in the normal micturition reflexes.

Animals↗
PubMed1982

Physiological tests during an improvement in riboflavin status in lactating Gambian women.

During several weeks riboflavin supplementation of lactating African women, which reduced their mean activation coefficient of erythrocyte glutathione reductase (EGRAC) from 1.65 to 1.21 and initiated an improvement in clinical deficiency signs, measurements were made of physiological functions which may be connected with riboflavin status. No specific response to the supplement could be detected in body weight, grip strength, haematological parameters, osmotic fragility and resistance to oxidative stress of erythrocytes, plasma iron levels and related indices, or plasma hormone levels. There was a cross-sectional relationship between erythrocyte distribution on Percoll density gradients and EGRAC before supplementation, and between the Percoll pattern and total haemoglobin concentration. It is not yet known, however, whether a direct causal relationship exists between these variables.

Adult↗
PubMedDate not supplied

The origin and distribution of neurons with projections passing through the inferior mesenteric ganglion of the guinea-pig.

Retrograde tracing with the fluorescent dye, Fast Blue, was used to examine the origin and distribution of neurons whose axons project through the inferior mesenteric ganglion (IMG) of the guinea-pig. These studies were performed by applying the tracer to (a) the rostral cut-end of the hypogastric nerves and (b) the caudal cut-end of the inter-mesenteric nerve (IMN). After application of tracer to the hypogastric nerves retrogradely labelled cell profiles were observed in the IMG and the superior mesenteric ganglion (SMG). The number of labelled cell profiles in the SMG was consistently about 15% of the number in the IMG. In only one of seven animals tested were labelled cells seen in the wall of the colon. Application of tracer to the IMN labelled cells in the IMG and in the wall of the colon. The distribution of the labelled enteric neurons was skewed towards the anal end of the colon. These results confirm that postganglionic sympathetic neurons in the SMG project axons through the guinea-pig IMG and describe the colonic distribution of enteric neurons that project through the IMG and into the IMN.

Amidines↗