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Biomedical subjects

S I Said

Publications and source records attributed to S I Said.

At least 19 recordsLinked to original sources
PubMed2006

Clues to VIP function from knockout mice.

We have taken advantage of the availability of vasoactive intestinal polypeptide (VIP) knockout (KO) mice to examine the possible influence of deletion of the VIP gene on: (a) airway reactivity and airway inflammation, as indicators of bronchial asthma; (b) mortality from endotoxemia, a model of septic shock; and (c) the pulmonary circulation. VIP KO mice showed: (a) airway hyperresponsiveness to the cholinergic agonist methacholine, as well as peribronchial and perivascular inflammation; (b) a greater susceptibility to death from endotoxemia; and (c) evidence suggestive of pulmonary hypertension.

Animals↗
PubMed2001

Regulation of apoptosis by vasoactive peptides.

Although originally discovered because of their ability to affect hemodynamics, vasoactive peptides have been found to function in a variety of capacities including neurotransmission, endocrine functions, and the regulation of cell proliferation. A growing body of evidence describes the ability of vasoactive peptides to regulate cell death by apoptosis in either a positive or negative fashion depending on the peptide and the type of target cell. The available evidence to date is strongest for the peptides endothelin, angiotensin II, vasoactive intestinal peptide, atrial natriuretic peptide, and adrenomedullin. Each of these peptides is discussed, with specific regard to apoptosis, in terms of regulatory activity, target cell specificity, and potential role in pulmonary physiology.

Adrenomedullin↗
PubMed2000

Pathways of inflammation and cell death in the lung: modulation by vasoactive intestinal peptide.

The pathogenesis of tissue injury in disease is a complex process that is only partially understood. We have investigated different models of acute lung injury, representing the clinical entity known as the acute respiratory distress syndrome, and tested their possible modulation by the neuropeptide vasoactive intestinal peptide (VIP). Three major mechanisms of injury appear to be involved in many of these models as common denominators: (1) activation of nuclear transcriptions factor NFkappaB; (2) apoptotic cell death; and (3) excitotoxic phenomena, due to activation of N-methyl-D-aspartate glutamate receptors. These pathogenetic mechanisms and pathways are logical targets of therapeutic intervention. Protection by VIP against lung injury, and against related forms of injury/cell death of neuronal cells and heart muscle, is attributable, in large measure, to the ability of VIP to suppress these mechanisms, and to additional anti-inflammatory and anti-oxidant actions. Finally, a hypothesis is presented for survival-promoting pathways that can be augmented by VIP and the related pituitary adenylyl cyclase-activating peptide.

Animals↗
PubMed2000

NMDA receptor activation: critical role in oxidant tissue injury.

The excitatory amino acid glutamate serves important neurologic functions, but overactivation of its N-methyl-D-aspartate (NMDA) receptor is toxic to neurons (excitotoxicity). We report that NMDA receptor blocker MK-801 (dizocilpine maleate) attenuated oxidant injury induced by paraquat or by xanthine oxidase. We conclude that excitotoxicity may be a key factor in oxidant tissue injury.

Animals↗
PubMed1998

Glutamate toxicity in the lung and neuronal cells: prevention or attenuation by VIP and PACAP.

VIP, which has been demonstrated to reduce or prevent oxidant injury in the lungs and other organs, is shown here to protect against excitotoxic injury of the lung and excitotoxic death of cortical neuronal cells in primary culture. Glutamate killing of neuron-like PC-12 cells, attributable to oxidant stress rather that to excitotoxicity, is also reduced or prevented by VIP and by the closely related peptide PACAP. The exact mechanisms of this protection remain to be determined, but appear to include antioxidant and anti-apoptotic actions, and suppression of glutamate-induced upregulation of its own receptor. Both VIP and PACAP offer the promise of novel and nontoxic means of defending against NMDA and glutamate toxicity.

Animals↗
PubMed1998

Enhancement of systemic and pulmonary vasoconstriction by beta-amyloid peptides and its suppression by vasoactive intestinal peptide.

(1) A beta peptides potentiate vasoconstriction, caused by norepinephrine, and possibly other endogenous vasoconstrictors. If this potentiation occurs in the cerebral circulation, close to sites of A beta deposition in AD brains, the enhanced vasoconstriction could result in neuronal ischemia and death. (2) By neutralizing this deleterious effect of A beta, and through other neuroprotective mechanisms, VIP may provide an important defense against neuronal loss in AD.

Amyloid beta-Peptides↗
PubMed1998

Vasoactive intestinal peptide inhibits human small-cell lung cancer proliferation in vitro and in vivo.

Small-cell lung carcinoma (SCLC) is an aggressive, rapidly growing and metastasizing, and highly fatal neoplasm. We report that vasoactive intestinal peptide inhibits the proliferation of SCLC cells in culture and dramatically suppresses the growth of SCLC tumor-cell implants in athymic nude mice. In both cases, the inhibition was mediated apparently by a cAMP-dependent mechanism, because the inhibition was enhanced by the adenylate cyclase activator forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine in proportion to increases in intracellular cAMP levels, and the inhibition was abolished by selective inhibition of cAMP-dependent protein kinase. If confirmed in clinical trials, this antiproliferative action of vasoactive intestinal peptide may offer a new and promising means of suppressing SCLC in human subjects, without the toxic side effects of chemotherapeutic agents.

1-Methyl-3-isobutylxanthine↗
PubMed1998

N-methyl-D-aspartate receptors are expressed by intrinsic neurons of rat larynx and esophagus.

Overactivation of N-methyl-D-aspartate receptors (NMDAR), a mechanism of central neurotoxicity, has recently been shown to increase airway responsiveness in rat lungs. NMDAR have not been localized in the airways, but neurons of the myenteric plexus in the rat express mRNA for NMDAR. Furthermore, a population of glutamate-containing cell bodies in the nucleus ambiguus projects to the rat larynx. On this basis, we hypothesized that some postganglionic parasympathetic neurons of the larynx, trachea and esophagus may express NMDAR. Sections of rat larynx, trachea and esophagus were immunocytochemically labeled for NMDAR subtype 2B using a specific antibody. NMDAR immunoreactivity was observed in cell bodies of individual neurons located in the submucosa and on the external surface of skeletal muscle in the larynx and also in neurons of the esophageal plexus. All NMDAR-positive nerve cell bodies also contained immunoreactivity for vasoactive intestinal peptide (VIP) and some were immunoreactive for nitric oxide synthase (NOS). None of the cell bodies of the tracheal plexus contained NMDAR immunoreactivity. The findings demonstrate that NMDAR are expressed in neurons of the rat larynx and esophagus and their activation may be associate with VIP or NO release.

Animals↗