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J S Davison

Publications and source records attributed to J S Davison.

At least 55 records · Page 3Linked to original sources
PubMed1993

Attenuated plasma extravasation to sensory neuropeptides in diabetic rats.

The effects of either substance P (SP) or a metabolically stable SP analogue, [pGlu5,Me-Phe8,Sar9]SP(5-11), alone or in combination with calcitonin gene-related peptide (CGRP) on blood pressure (BP) and extravasation of serum albumin were examined in normal and diabetic rats. CGRP (12 ng/kg) modified neither BP nor vascular permeability in control and diabetic rats. Both SP and its analogue (74 ng/kg) produced hypotension, and increased plasma extravasation in the respiratory tissues, urinary bladder and skin. The simultaneous injection of CGRP and SP resulted in modest potentiation of the vascular permeability actions of SP in control and diabetic rats. However, extravasation induced by [pGlu5,Me-Phe8,Sar9]SP(5-11) was potentiated by CGRP in control animals, but not in diabetic rats. Defective neurogenic inflammatory responses in diabetic rats may result from decreased responses in the effector tissues of diabetic rats to the neuropeptides released from sensory nerves.

Amino Acid Sequence↗
PubMed1993

Neural regulation of neutrophil involvement in pulmonary inflammation.

1. The high viscoelastic property of neutrophils is the major factor contributing to their extensive accumulation (more than 50% of circulating neutrophils) in the pulmonary microvasculature. 2. The cholinergic parasympathetic and adrenergic sympathetic nerves modulate the size of the pulmonary neutrophil pool by regulating arterial and venous pressures, increases in which promote or reduce neutrophil transit times, respectively. 3. Biochemical factors, such as the cytokines and complement, which act upon the neutrophils to increase their viscoelasticity and promote the interaction of neutrophil cell adhesion molecules with counter ligands on the endothelial cell, are the primary factors regulating the size of the pulmonary pool of vascular neutrophils. 4. The primary afferent nerves, through their release of substance P, are the most important neural elements regulating neutrophil accumulation and function. Substance P facilitates the actions of other inflammatory agents (e.g. LTB4, platelet activating factor) on neutrophil adhesion, migration and biochemical reactivity. 5. The sympathetic nervous system indirectly regulates neutrophil functions by regulating the release of an immunosuppressive factor from submandibular glands. 6. With continued, study of nervous system regulation of neutrophil function, the mechanisms by which psychological factors affect these cells will eventually be revealed.

Animals↗
PubMed1993

Spinal modulation of duodenal and colonic motility and arterial pressure by neuropeptide Y, neuropeptide Y fragment 13-36, peptide YY, and pancreatic polypeptide in rats: involvement of the cholinergic nervous system.

The pancreatic polypeptide-fold (PP-fold) peptides, peptide YY (PYY) and pancreatic polypeptide (PP) (200 pmol), increased duodenal intraluminal pressure following intrathecal (IT) administration into the thoracic (T8-T10) spinal cord of urethane-anesthetized rats. Neuropeptide Y (NPY), PPY, and PP (IT) increased colonic intraluminal pressure of rats. The excitatory effects of the PP-fold peptides, NPY and PYY, were accompanied by increases in mean arterial pressure (MAP) during the same time period followed by a decrease to hypotensive levels. There were no further alterations of duodenal or colonic pressure in rats during the hypotensive period. The effect of PP (IT) on MAP was characterized by a pattern of hypotension frequently followed by a hypertensive period. The modulation of duodenal and colonic pressure does not differ between the members of the PP-fold family of peptides; however, the effects of the different members of the PP-fold family of peptides on MAP were varied. The Y2 receptor ligand, NPY (13-36) (200 pmol) (IT), did not alter duodenal and colonic pressure or MAP in rats. Therefore, the effects of PYY and NPY in the thoracic spinal cord on duodenal and colonic motility may be mediated via Y1 (postjunctional) receptors. Atropine, a muscarinic antagonist, attenuated NPY's (IT) excitatory effect on colonic pressure but did not alter the MAP response to this peptide. Atropine did not modify PYY's (IT) regulation of duodenal and colonic intraluminal pressure. However, atropine did attenuate PPY's inhibitory effect on MAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Meal-induced c-fos expression in brain stem is not dependent on cholecystokinin release.

Sprague-Dawley rats injected with a "physiological" dose of cholecystokinin octapeptide (CCK-8; 6 micrograms/kg ip) expressed c-fos immunoreactivity in the nucleus of the tractus solitarius (NTS) and the area postrema (AP) of the brain stem. Injection of the CCK-A antagonist L-364,718 30 min before CCK-8 injection eliminated c-fos expression in these regions. These findings support the hypothesis that CCK-8 induced c-fos expression is mediated by CCK-A receptors. We then tested whether a meal (Isocal) could activate c-fos, and, if so, whether this response could be eliminated by L-364,718. Ingestion of Isocal induced c-fos immunoreactivity in the NTS and AP. Meal-induced c-fos expression was not blocked by the CCK-A antagonist L-364,718. These findings demonstrate for the first time that a purely physiological nonnoxious stimulus, a meal, induces c-fos in the rat brain stem and indicate that feeding induces c-fos expression by a pathway that is largely, if not entirely, independent of CCK release.

Animals↗
PubMed1993

Removal of the submandibular glands increases the acute hypotensive response to endotoxin.

We investigated the roles of the submandibular glands and of their sympathetic innervation on the acute hypotensive response induced by the i.v. injection of endotoxin (10 mg/kg; Salmonella typhosa) into rats anesthetized with sodium pentobarbital. Endotoxin given to unoperated and sham-operated rats induced a transient 30-40 mm Hg drop in blood pressure. Rats that had their submandibular glands removed (sialadenectomy) or bilateral resection of the superior cervical ganglia (ganglionectomy), exhibited significantly larger drops in blood pressure (approximately 65 mm Hg) that were maintained for the 60 min of the experiment. This increased responsiveness to endotoxin in sialadenectomized and ganglionectomized animals was not related to changes in haematocrit, white blood cell counts, or neutrophil activity. Pretreatment of rats with pentoxifylline (PTX) produced substantial protection against the hypotensive effects of endotoxin in ganglionectomized and sialadenectomized rats, although this xanthine did not affect the responses of sham-operated rats. These results suggest that the submandibular gland elaborates a factor that protects against acute hypotension induced by endotoxin and that this factor is under the control of the cervical sympathetic nervous system.

Animals↗
PubMed1992

The source of calcium for CCK-induced contraction of the guinea-pig gall bladder.

The sources of calcium for cholecystokinin octapeptide (CCK-OP)-induced gallbladder smooth muscle contraction are considered both extracellular and intracellular, but the relative need for intracellular calcium especially at low, physiological concentrations is not clear. To better define the calcium sources responsible for guinea-pig gallbladder contractions in vitro, we inhibited calcium influx using the calcium channel blocker, methoxyverapamil, and a calcium-free Krebs' solution. Availability and release of intracellular calcium stores were depleted by strontium substitution and ryanodine. CCK-OP was compared to bethanechol and potassium chloride (KCl). Preventing calcium influx with 10(-5) M methoxyverapamil depressed the responses to CCK-OP, bethanechol and KCl. Methoxyverapamil, however, had little effect on the time-dependent generation of tension to CCK-OP, but significantly reduced the response to bethanechol and KCl, each at ED50. The duration of the contractile response in the calcium-free Krebs' solution to CCK-OP was longer than that for bethanechol. Strontium (2.5 mM) significantly attenuated the response to CCK-OP and bethanechol, but not to KCl. Ryanodine significantly reduced contractions induced by CCK-OP but not for bethanechol, both at low dose ED25. These results indicate that contraction of the guinea-pig gallbladder induced by CCK-OP, bethanechol and KCl requires extracellular calcium influx. Further, the initiation and maintenance of contraction by CCK-OP and bethanechol necessitates calcium mobilisation from intracellular stores. CCK-OP may have a greater penchant for these calcium stores, particularly at physiological doses.

Animals↗
PubMed1992

Inhibition of neutrophil chemotaxis and activation following decentralization of the superior cervical ganglia.

Recent studies have shown that bilateral decentralization (sympathectomy) of the superior cervical ganglia (SCG) of rats sensitized to the parasite Nippostrongylus brasiliensis attenuated the development of pulmonary inflammation following allergen challenge. Sympathectomy inhibited total leukocyte infiltration into lung lavage fluids, particularly neutrophil infiltration. To define the effects of decentralization of the SCG on neutrophil responses, peripheral blood neutrophils of rats were isolated and tested in in vitro chemotaxis and phagocytosis assays. Neutrophils from rats that were sympathectomized 7 days previously displayed a marked reduction in chemotaxis to N-formyl-methionyl-leucyl-phenylalanine and leukotriene B4 compared to neutrophils from sham-operated or unoperated groups. Although the degree of chemotaxis was greater in blood neutrophils from parasite-infected rats than from uninfected rats, sympathectomy markedly reduced the chemotactic responses of both groups. In addition, neutrophils of sympathectomized rats were unresponsive to lipopolysaccharide-induced metabolic activation as assessed by in vitro phagocytosis and oxidative reduction of nitroblue tetrazolium. Thus, decentralization of the SCG of rats affects the chemotactic responses and functions of neutrophils. Understanding the role of the sympathetic nervous system in modulating the behavior of neutrophils will shed light on the interactions between the nervous and immune systems.

Animals↗
PubMed1992

Peptides in the gastrointestinal tract in human immunodeficiency virus infection. The GI/HIV Study Group of the University of Calgary.

The presence of immunoreactivity to the neuronal phosphoprotein B-50 and the peptides bombesin, calcitonin gene-related peptide, galanin, neurotensin, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal polypeptide was examined in biopsy specimens from the duodenum and rectum of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative male homosexual patients. The distribution of B-50 and the peptides was correlated with HIV serology, number of CD4+ lymphocytes, and the presence of HIV in biopsy culture. There was a very low incidence of enteric pathogens in both groups of patients. It was found that HIV-seropositive patients had a greater incidence of abnormal patterns of immunoreactivity (reduced intensity and/or density of innervation) in enteric nerves and enteroendocrine cells than HIV-seronegative patients. A reduction of substance P immunoreactivity was significantly correlated with reduced CD4+ lymphocyte count and HIV status; a similar trend was also seen for somatostatin and vasoactive intestinal polypeptide. Using B-50 as a marker, it was found that both groups of patients had altered patterns of immunoreactivity in rectal nerves. The findings of this study suggest that some of the clinical symptoms associated with HIV infection may be caused by a specific HIV enteropathy that influences enteric nerve and/or enteroendocrine cell function by altering the density of peptide immunoreactivity.

Adult↗
PubMed1992

Role for the submandibular gland in modulating pulmonary inflammation following induction of systemic anaphylaxis.

Previous studies have shown that bilateral decentralization of the superior cervical ganglia (SCG; decentralization) attenuates allergen-induced pulmonary inflammatory responses in male rats sensitized to the nematode Nippostrongylus brasiliensis. The present report examines the neuronal and glandular mechanisms mediating the protection against pulmonary inflammation afforded by decentralization. Tissues and organs innervated by the SCG are responsible for this protection since, in a manner similar to decentralization, bilateral removal of the SCG (ganglionectomy) reduced anaphylaxis-induced accumulation of inflammatory cells in bronchoalveolar lavage fluid. Removal of the submandibular gland (sialadenectomy) did not modify the severity of the pulmonary inflammation, but concurrent sialadenectomy and decentralization abolished the protective effect of decentralization. Thus, we postulate that cervical sympathetic nerves tonically inhibit release of anti-inflammatory factors from submandibular glands. No relationship was found between noradrenaline and serotonin content of submandibular glands and the degree of protection against pulmonary inflammation offered by decentralization and ganglionectomy. Both decentralization and ganglionectomy appeared to increase the level of transcripts that encode immunomodulatory growth factors (nerve growth factor and epidermal growth factor) in submandibular glands, but these denervations evidently did not modify the transcripts for TGF beta 2. Systemic inflammatory events are regulated by the central nervous system at a level superior to the SCG probably through modulation of immunoregulatory factors in submandibular glands.

Anaphylaxis↗
PubMed1992

Platelet activating factor and systemic anaphylaxis in Nippostrongylus brasiliensis-sensitized rats: differential effects of PAF antagonists.

1. The effects of two platelet-activating factor (PAF) antagonists, WEB 2086 and BN 52021, in reducing the changes in extravasation (Evans blue technique) and blood flow (radiolabelled microsphere method) to various organs and tissues following anaphylactic shock in the Nippostrongylus brasiliensis-sensitized rat were investigated. 2. Both antagonists attenuated anaphylaxis-induced increases in plasma protein leak in the trachea, stomach and small intestine, although they did not block extravasation in the colon and kidneys. 3. Anaphylaxis-induced decreases in blood flow to the adrenals were effectively antagonized by WEB 2086, although this antagonist did not reverse blood flow decreases to any other tissues. BN 52021, on the other hand, did not alter anaphylaxis-induced decreases in blood flow to the adrenals, but effectively prevented dramatic decreases in blood flow to the large and small bowel and spleen. 4. Anaphylactic shock produced marked reduction in blood pressure that was partly reversed by WEB 2086, whereas BN 52021 effectively blocked the decreases in cardiac output. 5. Thus, PAF is responsible for some of the haemodynamic and extravasation of protein changes associated with systemic anaphylaxis in the rat, although the differential inhibition observed with the two antagonists suggests that PAF alters vascular responsiveness through different mechanisms in selected tissues.

Anaphylaxis↗
PubMed1992

Cholecystokinin-induced c-fos expression in the rat brain stem is influenced by vagal nerve integrity.

Exogenous cholecystokinin (CCK) activates brain stem neurons in the area postrema and nucleus of the tractus solitarius, primarily in regions where vagal afferent fibres terminate. The present experiments show that vagal sensory fibres mediate CCK-induced c-fos in brain stem neurons, based on the findings that perivagal capsaicin pre-treatment in seven out of eight cases reduced or ablated c-fos expression in these regions.

Animals↗
PubMed1992

Differential sensitivities of the sphincter of Oddi and gallbladder to cholecystokinin in the guinea pig: their role in transsphincteric bile flow.

Cholecystokinin (CCK) is considered to simply contract the gallbladder and relax the sphincter of Oddi with meals. In this study, we examined this hypothesis by investigating the action of CCK on the sphincter of Oddi and gallbladder of the guinea pig. The experimental design used an in vitro preparation of the sphincter of Oddi to measure contraction of the circular muscle. CCK increased tone in both the gallbladder and the sphincter of Oddi in a concentration-dependent manner. The normalized concentration-response curves for CCK, however, revealed that the gallbladder had a greater sensitivity to CCK (ED50 7 nM) than the sphincter of Oddi (ED50 22 nM; p < 0.01). Conversely, the sphincter was more sensitive to bethanechol than was the gallbladder. When the sphincter of Oddi was stimulated maximally with CCK in the presence of atropine (10(-6) M) or tetrodotoxin (10(-6) M), the contractile response was significantly reduced (p < 0.05) although not abolished. Conversely, atropine completely abolished the responses to bethanechol (10(-3) M) and transmural field stimulation (70 V, 10 Hz, 1 ms, for 20 s). Transmural field stimulation of the sphincter that had been precontracted with CCK (26 nM) caused a transient, initial relaxation followed by contraction. Pretreatment with atropine augmented the duration of this relaxation, which could be completely abolished by tetrodotoxin. Thus, CCK contracts the sphincter of Oddi in the guinea pig by a direct (myogenic) and a neural (likely cholinergic) mechanism. Relaxation of the sphincter of Oddi also occurs in the guinea pig via noncholinergic inhibitory nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Hypothalamic neuropeptide Y inhibits gastric acid output in rat: role of the autonomic nervous system.

Injection of neuropeptide Y (NPY) into the hypothalamic paraventricular nucleus (PVN) inhibits gastric acid secretion in anesthetized rats. The role of the autonomic nervous system in mediation of this response was investigated. Unilateral microinjection of 200 pmol NPY into the PVN of anesthetized rats inhibited spontaneous and pentagastrin-stimulated gastric acid output. Inhibition was abolished by subdiaphragmatic vagotomy, atropine, and bethanechol but was restored by electrical stimulation of the distal cut end of the vagus in cervically vagotomized rats. Although sympathectomy, phenoxybenzamine, and yohimbine abolished the inhibition, it was not affected by prazosin treatment. Gastric blood flow was not altered by injection of NPY. These results suggest that the antisecretory effect of NPY in the PVN was sympathetically mediated via suppression of gastric vagal cholinergic tone through activation of alpha 2-adrenoceptors.

Animals↗
PubMed1992

Decentralization of the superior cervical ganglia and the immediate hypersensitivity response.

Bilateral decentralization of the superior cervical ganglia protects against pulmonary inflammation when measured 8 hr after induction of anaphylaxis in rats sensitized to the nematode, Nippostrongylus brasiliensis. Since anaphylactic shock produces immediate perturbations to the cardiovascular and respiratory systems, we examined whether bilateral decentralization of the superior cervical ganglia modified the responses of these two systems during the first 4 hr of the anaphylactic response. With the exception of the bronchioles, decentralization did not protect against anaphylaxis-associated increases in extravasation of albumin, and the small changes in respiratory function induced by anaphylaxis were unaffected by the denervation. Decentralization did not alter anaphylaxis-induced reductions in blood flow to the gastrointestinal tract; however, blood flow to the kidneys and spleen of decentralized rats was restored more rapidly to normal values. These results suggest that the protective effect of decentralization on the late phase pulmonary inflammation of anaphylaxis is unrelated to early changes in respiratory mechanics, although the protection may be facilitated by the more rapid re-establishment of normal cardiovascular homeostasis.

Analysis of Variance↗
PubMed1992

Role for the cervical sympathetic trunk in regulating anaphylactic and endotoxic shock.

This study tests the hypothesis that spinal nerves projecting down the cervical sympathetic trunk contribute to the regulation of systemic immune responses. Decentralization or ablation (ganglionectomy) of the superior cervical ganglia (SCG), which receive innervation from spinal segments C8-T8, were found to reduce the pulmonary inflammatory response consequent to induction of anaphylaxis in rats sensitized to the nematode Nippostrongylus brasiliensis. Furthermore, the hypotensive responses to IV endotoxin were attenuated in sensitized rats by these operations, whereas decentralization without ganglionectomy protected against endotoxic shock in normal (unsensitized) rats. These results suggest that systemic inflammatory events are regulated by the cervical sympathetic nervous system at a level superior to the superior cervical ganglia. Further studies are warranted to investigate the role of the cervical and thoracic sympathetic nerves in the regulation of systemic immunological function.

Anaphylaxis↗
PubMed1991

Intestinal mucin secretion in streptozotocin-diabetic rats: lack of response to cholinergic stimulation and cholera toxin.

In diabetic rats, intestinal mucin secretion is unusually high compared with that in normal rats. These studies demonstrate that mucin synthesis is also increased in the diabetic intestine. alpha- and beta-adrenergic agonists or antagonists did not affect mucin output in either normal or diabetic animals, suggesting that altered release in diabetes was not due to goblet cells responding abnormally to adrenergic agents. The cholinergic agonist bethanechol caused a dose-dependent and atropine-sensitive increase in mucin secretion from the normal intestine but had no effect on mucin release from diabetic tissue. Atropine alone did not reduce mucin secretion from the diabetic intestine to levels found in normal tissue. Cholera toxin caused an approximately fivefold increase in mucin output from normal rats but had no effect on mucin secretion from diabetic animals. Thus, goblet cell responses to cholinergic stimulation and cholera toxin in the diabetic intestine are markedly impaired. However, loss of cholinergic control does not appear to be responsible for altered baseline mucin secretion in diabetes.

Animals↗
PubMed1991

Capsaicin-sensitive vagal stimulation-induced gastric acid secretion in the rat: evidence for cholinergic vagal afferents.

1. The effects of electrical vagal stimulation on frequency-dependent gastric acid secretion were investigated in urethane-anaesthetized rats in vivo. 2. Stimulation at 4, 16 or 32 Hz was performed in rats treated with atropine (1 mg kg-1, i.v.), hexamethonium (10 mg kg-1, i.v. bolus and 1 mg kg-1 min-1, i.v. infusion) or atropine and hexamethonium (doses as above); in some experiments pentagastrin (1.2 micrograms kg-1 h-1, i.v. infusion) was infused prior to stimulation. 3. Maximal acid secretion occurred at 16 Hz. This was significantly reduced but not abolished by atropine or hexamethonium and completely abolished after atropine and hexamethonium. In the presence of pentagastrin, the acid secretory response to 16 Hz stimulation was augmented, atropine or hexamethonium reduced stimulated secretion by about 70%, whereas atropine and hexamethonium completely abolished stimulated secretion. 4. In rats in which the vagus nerve was pretreated with capsaicin 10-14 days before experimentation there was a significant reduction (by about 40%) in stimulated acid secretion at 16 Hz, which was virtually abolished by atropine treatment. After acute treatment of the vagus nerve with capsaicin (at the time of experimentation) maximally stimulated acid secretion was significantly reduced by about 50%. 5. Taken together, these results indicate that capsaicin-sensitive afferent fibres contribute to the acid secretory response induced by electrical vagal stimulation in the rat. Based on pharmacological evidence, the capsaicin-sensitive afferent fibres may be cholinergic, since atropine and hexamethonium totally abolish vagal stimulation-induced acid secretion.

Animals↗