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Biomedical subjects

G B Glavin

Publications and source records attributed to G B Glavin.

At least 37 records · Page 2Linked to original sources
PubMed1993

Vulnerability to stress ulcerogenesis in rats differing in anxiety: a dopaminergic correlate.

Dopamine and its agonists, acting through D1/DA1 receptors, have been shown to be effective protective factors against stress ulcerogenesis. Since anxiety has been related to stress ulcer development, we chose to examine dopaminergic activity in rats screened for the extremes of behaviorally manifest anxiety. High anxious rats develop more stress ulcers and more ethanol ulcers, relative to low anxious animals. High anxious rats require greater amounts of dopaminergic agonists for 50% protection against stress ulcer formation. In conditions of exposure to a stressor, high anxious rats lose amygdalar dopamine at a faster rate than do low anxious rats. These results suggest that anxiety is a significant factor in stress ulcer development and that central dopaminergic function is critically involved in mediating this pathogenetic factor.

Animals↗
PubMed1993

Use of a polypropylene mesh in fixing a chronic intracerebroventricular cannula.

Surgical implantation of an intracerebroventricular cannula allows investigators to determine the effects of central administration of compounds on physiological/pathological events taking place in the periphery. Attempts to examine the influence of repeated, chronic drug administration on gastrointestinal function have been hampered by the tendency of cannulae to become dislodged and lost during the course of such studies. We describe herein the insertion of surgical polypropylene mesh between the skull and the fixative during surgical implantation of an intracerebroventricular (i.c.v.) cannula. This inexpensive addition to a standard surgical procedure extends the period of time during which the cannula remains viable for i.c.v. drug administration. Extending the active life of the cannula, in turn, allows the investigator to reduce the number of animals used.

Animals↗
PubMed1993

Effects of neuropeptide Y and [Leu31,Pro34] neuropeptide Y on experimental gastric lesion formation and gastric secretion in the rat.

The present study examined the effects of neuropeptide Y (NPY) and a selective NPY1 receptor agonist, leucine31 proline34 neuropeptide Y ([leu31,pro34]NPY) on gastric lesion formation and gastric secretion in three preparations: Basal gastric acid secretion in conscious rats, restraint-induced gastric lesion formation and acid and pepsin output and gastric mucosal damage in pylorus-ligated rats. The hypothesis that benextramine, a non-selective NPY receptor antagonist, could attenuate responses to NPY or [leu31,pro34]NPY was also tested. Both NPY and [leu31,pro34]NPY (i.p. and i.c.v.) decreased basal gastric acid output, restraint-induced gastric lesion formation, and acid and pepsin secretion and gastric mucosal damage in pylorus-ligated rats. The magnitude of inhibition of secretion and of ulcer reduction was significantly greater for [leu31,pro34]NPY than for NPY at comparable doses. Benextramine blocked the protective effect of NPY and [leu31,pro34]NPY against restraint-induced gastric mucosal injury. Both central and peripheral treatment with benextramine blocked the antisecretory effects of centrally administered NPY and [leu31,pro34]NPY. These data were consistent with both a central and a peripheral action of NPY on the gut, possibly through Y1 receptors.

Adrenergic alpha-Antagonists↗
PubMed1992

Experimental gastric mucosal injury: laboratory models reveal mechanisms of pathogenesis and new therapeutic strategies.

Gastric ulcer is a multifaceted, pluricausal illness. Knowledge of the pathophysiology of gastric ulcer disease remains incomplete. Current pharmacological management of gastric ulceration is directed primarily at the reduction or neutralization of gastric acid secretion despite evidence that patients with this disease often exhibit normal gastric secretory activity. Attempts have been made to prevent or reduce gastric mucosal injury by cytoprotective agents without diminishing gastric acidity. We review several alternate explanations for the cause of gastric ulcers by examining various experimental models of gastric mucosal damage, including ethanol-, stress-, and nonsteroidal antiinflammatory drug-induced gastric lesions. We also discuss possible new strategies for the treatment of ulcer disease, particularly novel pharmacological targets arising from research conducted with these models. Growing realization that factors other than gastric secretion contribute significantly to the development of gastric ulcer disease prompts the conclusion that these same factors represent viable treatment alternatives.

Adenosine↗
PubMed1992

Parenteral domoic acid impairs spatial learning in mice.

The present study is the first to examine the effect of a single intraperitoneal injection of the neuroexcitotoxin domoic acid on learning in mice. Compared to saline controls, animals exposed to domoic acid (2.0 mg/kg) showed significant impairment on the acquisition of the place task in the Morris water maze. Observation of swim paths taken by mice searching for the underwater platform revealed a failure on the part of the domoic acid-exposed mice to select the appropriate problem solving strategies. The results, along with neuroanatomic work done here and elsewhere, suggest that impairment of acquisition and retention of this spatial navigation task by domoic acid, involves a neuropathology that includes not only the hippocampus, but other limbic, and possibly extralimbic brain regions.

Animals↗
PubMed1992

Central dopamine involvement in experimental gastrointestinal injury.

1. Rats were prepared with intracerebral cannulas for microinjection of test compounds into various brain regions. 2. Selective dopamine D1 agonists (SKF38393, SKF75670C) and a D1 antagonist (SCH23390) were injected into the cell body regions of the nigrostriatal, mesolimbic and mesocortical dopamine tracts or into a terminal field of these tracts (caudate nucleus, central nucleus of the amygdala and medial prefrontal cortex) prior to gastric ulcer induction by cold-restraint stress or duodenal ulcer induction by cysteamine. 3. The dopamine D1 agonists reduced both stress gastric ulcers and duodenal lesions most significantly when given into either the cell body region or a terminal field of the mesolimbic DA tract with much less effects seen for the nigrostriatal tract. 4. No effects were seen upon infusion of the agonists into the mesocortical cell body or terminal field regions. 5. The D1 antagonist worsened both stress-induced gastric lesions and duodenal lesions if given into mesolimbic regions and, to a much lesser extent when injected into the nigrostriatal tract. 6. No effect of the D1 antagonist was seen upon administration into the mesocortical tract. 7. Central dopamine D1 receptors, particularly in the mesolimbic DA tract, appear to be involved in mediating the gastrointestinal consequences of exposure to stress.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Dopamine: a stress modulator in the brain and gut.

1. Central dopamine (DA) exhibits large and rapid responses to stress challenge, particularly in the mesolimbic DA tract and, to a lesser degree, in the mesocortical tract. 2. Over the last few years, there has emerged an increasing role for peripheral DA, especially gastrointestinal DA, as a modulator of gastroduodenal injury consequent to stress exposure. 3. Evidence has accumulated which strongly supports a role for DA as an endogenous gastroprotective element and it appears that the dopaminergic "brain-gut axis" is a critical determinant of gastroduodenal mucosal integrity in the stress-challenged gut.

Animals↗
PubMed1992

Brain-gut relationships: gastric mucosal defense is also important.

Growing recognition that there exists a functionally important brain-gut axis has prompted several research groups to examine more closely the role of central nervous system factors in gastric mucosal injury. Less attention has been directed toward brain regulation of defensive factors in the gut. Toward that end, we have been characterizing a growing role for dopamine as an important mediator of gastric defense. New data suggest that dopamine, and other substances including many peptides as well as interleukin, act not only to reduce aggressive elements which promote gastric mucosal injury (gastric acid, pepsin, gastrin, leukotrienes) but also to augment defensive factors which retard ulcerogenesis (mucus, bicarbonate, prostaglandins, free radical scavenging enzymes, vasodilators/relaxers). Increasing attention should be directed toward the often-neglected defensive aspect of gastric mucosal ulcerogenesis and protection.

Animals↗
PubMed1991

Adrenalectomy, but not vagotomy, reverses the worsening effect of Ca2+ blockers on ethanol-induced gastric lesions in rats.

This study examines the influence of the adrenals and of the vagus nerve on the lesion-worsening action of nitrendipine or verapamil on 75% ethanol-induced gastric mucosal damage in rats. Bilateral adrenalectomy antagonized ethanol lesion aggravation by nitrendipine or verapamil; instead, dose-related lesion reduction was seen. Dexamethasone treatment of adrenalectomized rats restored the lesion-enhancing effects of both Ca2+ channel blockers. Bilateral subdiaphragmatic vagotomy failed to abolish the adverse action of nitrendipine or verapamil on ethanol lesions. The findings suggest that the adrenal corticoids modulate the worsening effect of Ca2+ channel antagonists on ethanol-induced gastric damage; when the influence of the adrenal steroids is removed, these compounds become gastroprotective.

Adrenalectomy↗
PubMed1990

Dopamine in gastrointestinal disease.

Dopamine is an important enteric neuromodulator. Herein we review the data that support a role for dopaminergic involvement in experimental duodenal and gastric ulceration; gastric, pancreatic, and duodenal secretion; gastrointestinal motility; and gastric and intestinal submucosal blood flow regulation. There also is support for a role for dopamine and dopamimetic agents in the treatment of certain experimental gastrointestinal diseases because some highly selective dopamine agonists are gastroprotective when given either parenterally or centrally. Based upon these observations, we suggest that dopamine is a key element of the "brain-gut axis" and represents a potentially important target for pharmacotherapeutic exploitation.

Animals↗
PubMed1990

Effects of metkephamid (LY127623), a selective delta opioid receptor agonist, on gastric function.

Metkephamid, a delta opioid receptor agonist, blocked cold-restraint stress ulcers, reduced absolute ethanol-induced gastric ulcers and, at the lowest and highest doses examined, reduced basal gastric acid secretion in conscious rats, all to a significant degree. The dose effects on stress ulcer formation parallel those seen against maximal electroshock seizures and suggest that both central as well as peripheral delta opioid receptors mediate gastrointestinal responses to stress.

Animals↗
PubMed1990

Domoic acid-induced neurovisceral toxic syndrome: characterization of an animal model and putative antidotes.

A rodent model of neurovisceral toxic syndrome induced by the neuroexcitant amino acid, domoic acid, is described, along with the activity of a putative antidote, the nonselective excitotoxin antagonist, kynurenic acid. Both an extract of contaminated mussels and pure domoic acid induced a characteristic syndrome including: sluggishness, scratching stereotypy, convulsions and death. Autopsy revealed gastric and duodenal lesions and peritoneal ascites. Kynurenic acid significantly obtunded these behavioral and physiological effects, particularly when given 60-75 min after the toxic insult. Probenecid, a blocker of organic acid transport, and tryptophan, a precursor of endogenous brain kynurenic acid, increased the time frame in which kynurenic acid exerted its protective effects. Kynurenic acid alone, in nontoxin-challenged animals significantly blocked cold-stress gastric lesions, significantly reduced basal gastric acid secretion and was protective to a lesser degree against ethanol-induced gastric mucosal injury. The murine model of domoate toxicity represents an inexpensive, reliable and sensitive biological assay for screening commercial shellfish for excitotoxin contamination. We are currently exploring kynurenic acid and other compounds for possible therapeutic use in both current and any future victims of neuroexcitant amino acid toxicosis.

Animals↗