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Biomedical subjects

J S Davison

Publications and source records attributed to J S Davison.

At least 73 records · Page 4Linked to original sources
PubMed1991

The effect of intracisternal injection of thyrotropin-releasing hormone on gastric and duodenal motility in the urethane-anaesthetized rat.

Intracisternal injection of thyrotropin-releasing hormone (TRH; 1-3 micrograms) caused an increase in gastric motility and usually an inhibition of duodenal motility. These effects were abolished by vagotomy and atropine. No inhibition was seen even after tone and motility had been restored to a point at which vagal stimulation could evoke profound inhibition of gastric and duodenal motility. It is concluded that TRH is a specific activator of enteric excitatory pathways and that duodenal inhibition seen in control animals is a consequence of gastro-duodenal inhibitory reflexes.

Animals↗
PubMed1990

Marked antiinflammatory effects of decentralization of the superior cervical ganglia.

Intravenous challenge with parasite antigens in Nippostrongylus brasiliensis-sensitized rats resulted in anaphylactic shock and, in some animals, death. Surviving animals showed significant drop in mean arterial blood pressure, cardiac output, and blood flow to the trachea, bronchioles, and mesentery. After anaphylaxis, changes in the cellular and protein composition in bronchoalveolar lavage fluids (BALF) were assessed. 8 h after antigen challenge, there was significant influx of inflammatory cells and an increase in the levels of histamine and serum-derived immunoglobulins (IgG and IgM) in BALF. Chemotactic activity for neutrophils was also present in BALF. Once we established this anaphylaxis-induced model of pulmonary inflammation, we sought to determine whether or not the superior cervical ganglia (SCG) modulate this inflammation. We performed bilateral superior cervical ganglionectomy or decentralization of the SCG. Our results show that decentralization significantly reduced mortality (by 68%) after anaphylaxis. Furthermore, the increases in levels of serum-derived proteins, histamine, and influx of cells (especially neutrophils) observed in BALF after anaphylaxis were attenuated by both decentralization and ganglionectomy. By contrast, hemodynamic parameters in the respiratory tract and the presence of neutrophil chemotactic activity in BALF were not influenced by decentralization. Thus, the severity of pulmonary inflammation initiated by systemic anaphylaxis is depressed by bilateral ganglionectomy or decentralization of SCG.

Animals↗
PubMed1990

Effects of substance P and vasoactive intestinal polypeptide on contractile activity and epithelial transport in the ferret jejunum.

Previous studies in the ferret demonstrated that vagal nerve stimulation induced an atropine-resistant water secretion. Substance P and vasoactive intestinal polypeptide are possible mediators of this secretory response. The objectives of this study were to investigate the in vivo effects of substance P and vasoactive intestinal polypeptide on the jejunal musculature and epithelium. Substance P caused an increase in jejunal motility, water secretion, and transmural potential difference. Cholinergic blockade did not affect the substance P-induced contractions, but did reduce the increase in transmural potential difference, suggesting an inhibition of water secretion. Vasoactive intestinal polypeptide abolished motor activity; however, it induced an increase in transmural potential difference that was atropine and tetrodotoxin resistant. By immunohistochemical methods, immunoreactive vasoactive intestinal polypeptide and immunoreactive substance P were localized to both nerve cell bodies and nerve fibers in the ferret intestine. Determination of intestinal concentrations of vasoactive intestinal polypeptide and substance P in the ferret showed concentrations of these two neuropeptides that were similar to those in human intestine and demonstrated much higher concentrations of these substances in the muscular layer than in the epithelial layer. Our data demonstrate that in the ferret substance P excites and vasoactive intestinal polypeptide inhibits jejunal motor activity. However, both peptides increase water secretion. Our results suggest that in response to vagal stimulation, neuronally released substance P or vasoactive intestinal polypeptide may participate in the atropine-resistant water secretion.

Action Potentials↗
PubMed1990

Alterations in regional blood flow in rats following sensitization to the nematode Nippostrongylus brasiliensis: effects of PAF antagonists.

1. Changes in tissue and organ blood flow associated with sensitization of rats to the nematode parasite, Nippostrongylus brasiliensis, were studied 30 to 35 days after infection, a time when very few worms remain in the animal. 2. Neither active nor passive sensitization modified heart rate, mean arterial blood pressure, cardiac output or total peripheral resistance. Passive sensitization and administration of non-immune sera did not modify blood flow to any of the tissues studied. 3. Active sensitization increased hepatic arterial blood flow, but decreased blood flow to the stomach, duodenum, jejunum and the submandibular glands. These effects cannot be attributed to residual nematode infections as treatment with the anthelmintic, thiabendazole, did not alter blood flow relative to untreated, actively sensitized rats. 4. The effects of active sensitization on blood flow were probably due to an action of platelet-activating factor (PAF) since treatment of actively sensitized animals with the selective antagonists, WEB-2086 and BN 52021, reversed the decrease in flow seen to the intestinal regions. The PAF antagonists increased blood flow to the kidneys and the trachea of sensitized animals. 5. These results suggest that the PAF released from undetermined sources in nematode-sensitized rats, produces altered blood flow, primarily to the stomach and proximal small bowel.

Animals↗
PubMed1990

Hemodynamic changes associated with anaphylaxis in parasite-sensitized rats.

Thirty days after infection with the parasite Nippostrongylus brasiliensis, microcirculatory changes associated with worm allergen-induced anaphylactic shock in pentobarbital-anesthetized rats were studied. Allergen challenge decreased heart rate, mean arterial blood pressure, and cardiac output (CO) for 60 min, although CO increased markedly by 240 min. Blood flow (ml.min-1.g wet tissue-1) was reduced to most tissues, with the exception of the kidneys, hepatic arterial, heart, and brain, for 60 min. Depressed flow to the adrenals and enhanced flow to the kidneys, trachea, stomach, and mesentery were observed at 240 min. The percent distribution of cardiac output per gram wet tissue (%CO/g) increased initially to the kidneys, heart, liver, and cervical spinal cord, decreased to the spleen and cecum, and remained unchanged to other gastrointestinal tissues. The %CO/g to most tissues returned to normal by 60 min but decreased to the adrenals at 240 min. The intestine is an important organ affected by anaphylaxis in the rat, and the liver may participate in alleviating anaphylaxis.

Anaphylaxis↗
PubMed1989

Effects of streptozotocin-diabetes on rat intestinal mucin and goblet cells.

Intestinal mucin and goblet cells were examined in streptozotocin-diabetic rats and age-matched controls. Mucin (tissue content and secretion) was measured using a highly specific enzyme-linked immunoassay. In contrast to the increased protein to deoxyribonucleic acid ratio, an absolute decrease was observed in the mucin to deoxyribonucleic acid ratio in mucosal homogenates of the diabetic intestine. This was not due to a loss of goblet cells as their numbers per crypt-villus unit increased in diabetic rats (in proportion to the rise in enterocyte numbers and crypt-villus length). Histochemically, goblet cell mucin was unchanged in diabetes. After a 90-min incubation of everted intestinal segments in Krebs' buffer, pH 7.4, at 37 degrees C, the amount of mucin released into the medium was the same in diabetic and control rats when expressed relative to tissue deoxyribonucleic acid. However, secreted mucin represented a significantly larger proportion of the total tissue mucin content in diabetic animals. Thus, to maintain mucin output at normal levels, the rate of mucin secretion is apparently increased in the diabetic intestine, despite (or perhaps causing) a large decrease in the tissue mucin content.

Animals↗
PubMed1989

Regulation of epithelial transport in the jejunal mucosa of the guinea pig by neurokinins.

This study characterizes the actions of the neurokinins and calcitonin-gene related peptide (CGRP) on electrolyte transport across the mucosa of the guinea pig jejunum in vitro in a modified Ussing chamber. By following changes in short circuit current (Isc) induced by substance P (SP) and neurokinins A & B (NKA & NKB) in the presence and absence of tetrodotoxin (TTX) and atropine, it was established that two distinct neurokinin receptors are involved in the regulation of electrolyte transport. NKA preferentially activates a neuronal receptor since the actions of this neurokinin were inhibited by both TTX and atropine. SP, whose actions were reduced to a lesser extent by TTX and atropine, is considered to activate preferentially a receptor on the epithelial cells. The third neurokinin, NKB, appears to act non-selectively on both the neuronal and epithelial receptors. CGRP, which per se did not affect Isc, markedly potentiated the increases in Isc induced by SP and NKB, and thus acts synergistically with the epithelial neurokinin receptor. These results suggest that two distinct neurokinin receptors (the NK-1 and the NK-2) regulate epithelial transport in the jejunal mucosa of the guinea pig, and furthermore indicate that at least one of the peptides found in enteric nerves (i.e. CGRP) modulates the actions of neurokinins on epithelial cells.

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

Gastric response to mucosal IgE-mediated reactions.

The effect of immunoglobulin E (IgE)-mediated anaphylaxis has been extensively studied in the small intestine, but little information is available on the response of the stomach to IgE-mediated mucosal reactions to food proteins. The effect of luminal antigenic challenge on gastric acid secretion, gastric emptying, and mucosal mast cell degranulation was examined in rats sensitized to egg albumin or in sham-treated controls. Intraluminal challenge of the stomach with egg albumin in sensitized animals significantly increased gastric acid secretion and delayed gastric emptying. The response was specific for the sensitizing antigen as challenge with bovine serum albumin was without effect. Sham-treated animals showed no response to egg albumin or bovine serum albumin. The increase in gastric acid secretion was reproduced by antigen challenge in naive animals passively transferred with hyperimmune serum. This effect was abolished by prior heat treatment of the serum. In sensitized animals challenged with egg albumin, there was histological evidence of mast cell degranulation in the stomach mucosa, increased intraluminal release of histamine, and increased serum levels of rat mast cell protease II, a marker specific for mucosal mast cell degranulation. The findings indicate that the stomach is a target organ for IgE-mediated reactions to food proteins. Antigen challenge in sensitized animals leads to increased gastric acid secretion and delayed emptying and evidence of mucosal mast cell activation.

Animals↗
PubMed1988

Intracellular pH influences the resting membrane potential of isolated rat hepatocytes.

This study in isolated rat hepatocytes sought to determine if the changes in membrane potential associated with intracellular alkalinization or acidification could be attributed to changes in K+ conductance. Intracellular pHi was manipulated using the 'NH4+-pulse' method: inducing intracellular alkalinization with NH4Cl (10 mM), and producing acidification by diluting the NH4+-loaded cells with ammonium ion-free buffer or by adding sodium proprionate. Membrane potential and resistance were measured in freshly isolated rat liver cells using intracellular microelectrodes. The results indicated that intracellular alkalinization was associated with hyperpolarization and decreased membrane resistance, whereas intracellular acidification caused depolarization with increased membrane resistance. As pHi-mediated electrogenic responses have been related to changes in K+ conductance in other epithelial tissues, the influence of K+ transport inhibitors on NH4+-evoked electrical effects was examined. NH4Cl-evoked membrane potential changes were inhibited by the K+ channel blockers, quinine and barium and in potassium depolarized cells (cells bathed in a high K+ medium where [K+]in = [K+]out = 140 mM). Furthermore, Rubidium-86 (86Rb+) efflux from preloaded hepatocytes, a measure of K+ permeability, was enhanced following intracellular alkalinization but inhibited by intracellular acidification. Thus, these results indicate that pHi-evoked electrogenic effects in hepatocytes are mediated through changes in K+ conductance.

Ammonium Chloride↗
PubMed1988

Injection of neuropeptide Y into the paraventricular nucleus of the hypothalamus inhibits gastric acid secretion in the rat.

Neuropeptide Y (NPY) was injected into the paraventricular nucleus (PVN) of the hypothalamus of anesthetized rats in order to assess its effect on gastric acid secretion. NPY evoked a dose-dependent decrease of interdigestive gastric acid output when injected directly into the PVN or immediately ventral to it. Intracerebroventricular NPY and saline injections did not alter acid output. Injection of NPY into adjacent non-PVN hypothalamic areas resulted in either an elevated acid output or had no effect depending on the site of injection. Mean arterial blood pressure and heart rate were not consistently affected by NPY. These results show that injection of NPY into the PVN of anesthetized rats inhibits interdigestive gastric acid output in a dose-dependent manner.

Animals↗
PubMed1988

Altered regulation of intestinal ion transport by enteric nerves in diabetic rats.

We compared ion transport parameters in isolated ileal mucosa from diabetic rats (8 wk after streptozotocin injection) and littermate controls under basal conditions and in response to electrical transmural stimulation (TS). Stripped ileal mucosa (submucosal plexus intact) was mounted in Ussing flux chambers modified to include stimulating electrodes on opposite sides of the tissue. Under basal conditions unidirectional fluxes of Na+ and Cl- were decreased across mucosa from diabetic rats compared with controls, whereas net fluxes were not significantly different. TS caused a tetrodotoxin (TTX)-sensitive transient increase in short-circuit current (Isc) that was significantly less in tissue from diabetic than control rats. The muscarinic cholinergic receptor antagonist, atropine, significantly reduced the Isc response to TS in ileum from control but not diabetic rats. In addition, the noncholinergic component of the response was smaller. The muscarinic agonist, Urecholine chloride (bethanechol chloride), caused an increase in Isc that was unaffected by pretreatment with TTX and was the same in tissue from control and diabetic rats. Our results suggest that the intestinal abnormalities that occur in diabetes may include a defect in the regulation of ion transport by enteric nerves resulting in an abnormal ability to respond to luminal and other stimuli.

Animals↗
PubMed1988

Mechanical properties and sensitivity to CCK of vagal gastric slowly adapting mechanoreceptors.

Sixty single afferent fibers with endings in the stomach wall were isolated from the cervical vagus of urethan-anesthetized Sprague-Dawley rats. All the fibers, most of which were spontaneously active, increased their discharge after gastric distension or during spontaneous contractions of the stomach. Because of this and the characteristic dynamic and static features of their response to inflation and deflation, they were identified as in-series tension receptors. Certain features of their responses, previously suspected from studies on reflex modulation of vagal efferent fibers or brain stem neurons, were directly confirmed. These included a broad range of mechanical thresholds and spontaneous firing frequencies that were correlated and a sensitivity only to dynamic stretch and active contraction in the highest threshold endings. The tension receptors could also be activated by circulating cholecystokinin, an effect unrelated to changes in intraluminal pressure and hence gastric wall tension, suggesting that there may be humoral modulation of visceral sensory signals that might be relevant to several behavioral situations, such as food intake regulation.

Animals↗
PubMed1988

Inhibition of breathing associated with gallbladder stimulation in dogs.

The effect of mechanical stimulation of the gallbladder on breathing was studied in anesthetized spontaneously breathing dogs. Measurements of tidal volume, breathing frequency, rib cage and abdominal diameter, transdiaphragmatic pressure, and electrical activity of the diaphragm were made while traction or compression was applied to the gallbladder for periods of 30 s. Both forms of mechanical stimulation produced similar changes, including large decreases in tidal volume, respiratory rate, electrical activity of the diaphragm, and transdiaphragmatic pressure swings. Inspiratory rib cage expansion was little affected, but abdominal expansion was greatly reduced, and swings in gastric pressure were reduced more than swings in pleural pressure, indicating a selective decrease in diaphragmatic activity. Recovery of all measured parameters returned toward control values, despite continued traction or compression. Some inhibition persisted after the stimulus was withdrawn. The very brief interval between stimulus and response suggested that the mechanism was a neural reflex. The afferents involved are unknown but are not purely vagal in nature, since qualitatively similar results were seen in animals after vagotomy. The alteration in breathing frequency indicates that at least part of the reflex is supraspinally mediated. The change in pattern of breathing closely resembles that seen in subjects after abdominal surgery and supports the theory that reflex inhibition of breathing contributes to postoperative pulmonary complications seen in those subjects.

Animals↗
PubMed1988

Effect of chlorpromazine (CPZ) on cholecystokinin-induced gallbladder contraction: the role of calcium.

Smooth muscle contraction is initiated by a rise in intracellular calcium, which binds to calmodulin resulting in myosin phosphorylation. CPZ impairs smooth muscle contraction by either interfering with calcium influx at low concentrations (less than 1.25 x 10(-5) M) or inactivating calcium-calmodulin at higher levels. This chlorpromazine effect was used to determine if gallbladder agonists act through different intracellular mechanisms. Guinea pig gallbladders were mounted in an organ bath and auxotonic contractions induced by bethanechol, KCl and the octapeptide of cholecystokinin (CCK). Bethanechol and KCl-induced contractions were profoundly inhibited by 1.25 x 10(-5) M CPZ throughout the dose-response curve. In contrast, CPZ did not affect CCK-mediated contractions at CCK concentrations less than 5.7 x 10(-8) M. At maximal CCK doses (3 x 10(-7) M), CPZ had only a modest inhibitory effect of 20%, compared with tension losses of 62 and 80% for bethanechol and KCl, respectively. This inhibition with high-dose CCK was offset by increasing extracellular calcium in the organ bath. The resistance of CCK to CPZ inhibition at low doses within the physiologic range implies that CCK acts independently of extracellular Ca2+ unlike the other agonists. Higher CPZ concentrations, greater than or equal to 1.25 x 10(-4) M, markedly suppressed CCK throughout the dose-response curve. Cholecystokinin may act via myosin phosphorylation, but unlike other agonists any rise in cytoplasmic calcium likely originates from an intracellular site.

Animals↗
PubMed1988

Modified smooth muscle responses of jejunum in streptozotocin-diabetic rats.

Complications of the gastrointestinal tract in patients with diabetes mellitus can cause marked discomfort and may modify the ability of the patient to maintain normal glucostasis. In an attempt to elucidate some of the factors causing gastrointestinal dysfunction in experimental diabetes we examined the responses of jejunal smooth muscle in streptozotocin-induced diabetes in rats to some of the neurotransmitters and autocoids found in the enteric nervous system. Jejunal tissues from 4- to 5-week diabetic rats were examined for their responses to neurokinin (NK) A, NKB, substance P (SP), bradykinin, neurotensin, bethanechol, isoproterenol and phenylephrine. The affinities for all these agonists, except for SP which increased slightly with diabetes, were the same in both control and diabetic tissues. NKA was the most potent neurokinin and elicited the largest contractile responses from jejunal tissues of both control and diabetic animals. The contractile response to NKA, but not that to NKB or SP, was increased in the jejunum from diabetic animals. Part of this increased responsiveness was antagonized by atropine. The contractile effects of the cholinergic agonist, bethanechol, were not altered by the diabetic state. Decreased relaxation responses in the jejunum from diabetic animals were observed for bradykinin, neurotensin and isoproterenol, but not for phenylephrine. These results suggest that the myogenic actions of several agonists are modified in experimental diabetes.

Animals↗