Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sharp pain is conducted rapidly by myelinated delta A fibers and diffused pain slowly by nonmyelinated C fibers to pseudobipolar neurons in the posterior ganglion and from there to neurons located in the posterolateral horn of the spinal cord. From here on nociferous impulses are transmitted by excitatory peptides (e.g. substance P) or amino acids (e.g. glutamate, aspartate) through interconnecting neurons of the pain pathways, primarily on the contralateral side, to the brain stem and from there to the sensory cortex, where they are appreciated and acted upon. There are specific inhibitory receptors located on axon terminals, near to the release sites of the excitatory amino acids and peptides. Stimulation of these receptors by their appropriate ligands such as endogenous (e.g. enkephalis, endorphins) or exogenous opioids, clonidine, serotonin, somatostatin inhibits the release of excitatory neurotransmitters and relieves pain. There are at least 3 different opioid receptors, called mu-, kappa- and delta-receptors in the spinal cord. These can be differentiated from one another by their specific affinity toward different endogenous or exogenous opioids and the pure narcotic antagonist, naloxone. It appears that the nociferous impulses transmitted by parallel pathways equipped with different inhibitory receptors have to be integrated to produce pain sensation and partial inhibition of transmission in different pathways or complete inhibition in one of the pathways may relieve pain. In recent years the concept of "selective spinal analgesia" has been applied clinically for the relief of postoperative, obstetrical and chronic pain. At first it was expected that the intrathecal or peridural administration of morphine will produce analgesia without the side effects of systemically administered morphine. It soon became evident, however, that intrathecally and peridurally administered morphine after several hours of delay reaches the fourth ventricle and by stimulating mu-receptors may cause respiratory depression and other undesired effects (e.g. nausea, vomiting, pruritus). Several different approaches are being investigated for the production of selective spinal analgesia without side effects. They include: a. the use of more lipophilic, long-lasting opioids (e.g. lofentanil) which would be almost completely absorbed by the spinal cord and therefore would not reach the medullary centers; b. the development of opioids with specific affinity to kappa- and for delta- and little or no affinity to mu-receptors, primarily responsible for side effects; and c. combining lower doses of opioid agonists with alpha 2-adrenergic agonists (e.g. clonidine) or with somatostatin. It is conceivable that in the not-too-distant future, it will be possible to achieve through these measures, selective spinal analgesia without side effects.
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PMID:Pain control with intrathecally and peridurally administered opioids and other drugs. 168 73

Substance P is a 11 amino-acids peptide which belongs to the tachykinins, a family of peptide which induces a rapid contraction of the smooth muscle of the digestive tract. The occurrence of substance P has been demonstrated by immunohistochemical and radioimmunological techniques in most parts of the central and peripheral nervous system. Substance P exerts on the smooth muscle of all the areas of the digestive tract a strong excitatory effect which is either direct or relayed by the cholinergic intramural neurones. Numerous electrophysiological, pharmacological and immunohistochemical data lead to the conclusion that substance P is released by intrinsic neurones of the digestive tract or by extrinsic nerves (vagus and splanchnic nerves, etc...). This release is enhanced by acetylcholine, cholecystokinin, serotonin and neurotensin, it is reduced by opioid peptides and noradrenaline. Substance P participates in the intestinal peristaltic reflex by the activation of the smooth muscle cells of the intestine, either directly or through the activation of the cholinergic intrinsic neurones. Substance P is also involved in the genesis of a non-cholinergic ascending excitatory activity likely occurring during vomiting. Lastly, substance P participates in the reflex contraction of the lower oesophageal sphincter following acidification of the distal part of the oesophagus.
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PMID:[Role of substance P in the nervous system control of digestive motility]. 172 Jun 93

The newly recognized class of 5-hydroxytryptamine receptors (5HT3) may be involved in the induction of nausea, since their pharmacological antagonists are effective against emesis induced by chemotherapy. 5HT3 receptors are present on enteric neurons, and 5HT3 blockers may produce mild constipation; we thus hypothesized that 5HT3 receptors would modulate colonic motility. To determine if GR 38032F, a selective 5HT3 antagonist known to have antiemetic effects, influences colonic transit in health, a randomized, double-blind, placebo-controlled crossover study was performed. Using a radiopaque marker technique, colonic transit was quantified in 39 healthy volunteers (19 men, 20 nonpregnant women) 18-70 years of age. On a standard 25-g fiber diet, 16 mg of GR 38032F was given orally thrice daily. Gastrointestinal peptides (peptide YY, human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, substance P) were also measured in plasma fasting and postprandially. Mean total colonic transit time on placebo was 27.8 hr, while on GR 38032F it was 39.1 hr (P less than 0.0005). Transit times through the left colon (P less than 0.0005) and rectosigmoid (P less than 0.05) were prolonged by the drug, but right colonic transit was not significantly altered. Transit times did not correlate with age or gender, but subjects with shorter transit times were significantly more affected than were those with longer transit times. The peak release of peptide YY was minimally decreased following GR 38032F (P less than 0.01), but the peak and integrated postprandial responses of human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, and substance P were not significantly altered by the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GR 38032F (ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man. 213 32

Three patients suffering from an absence of the enteric nervous system are reported. Two sisters presented with severe vomiting shortly after birth and dilatation of the intestine proximal to a stenosis. There was an absence of the enteric nervous system throughout the entire length of the intestine distal to the duodenum. A boy presenting an ileus was found to suffer from an aganglionosis of the entire colon. There was also an absence of neuronal bodies and nerve fibers in the small intestine. The final diagnosis was made by histochemical and immunocytochemical stains for acetylcholinesterase, lactate hydrogenase, neuron-specific enolase, protein S-100, and substance P. In the literature, 13 other patients have been reported. On the basis of differences of symptoms, incidence, sex ratio, genetics, and, presumably, pathogenesis between absence of the enteric nervous system and aganglionosis, it is assumed that the two diseases are separate entities.
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PMID:Absence of the enteric nervous system in the newborn: presentation of three patients and review of the literature. 351 82

Short-latency emetic responses were induced in dogs by injecting angiotensin II (AII), arginine vasopressin (AVP), and neurotensin (NTN) into cerebroventricular (ICV) and cisternal (ICT) sites also responsive to the emetic effects of apomorphine (APO). Angiotensin III, bradykinin, bombesin, oxytocin, adrenocorticotropic hormone, substance P, gastrin-related peptide and cholecystokinin were ineffective. The results suggest a possible dopaminergic mediation of peptide-induced emesis by receptors in the area postrema (AP).
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PMID:Emetic effects of centrally administered angiotensin II, arginine vasopressin and neurotensin in the dog. 404 79

The responses of 122 neurons in the area postrema of anesthetized dogs to 17 common transmitters and peptides were determined. Recordings were made from one barrel of a seven-barrel ionophoretic electrode. All neurons were silent at rest, but most could be detected and excited by the application of glutamate. The glutamate response was a brief, high-frequency response of less than 1-sec duration. Excitatory responses were also found to histamine, norepinephrine, serotonin, dopamine, apomorphine, angiotensin II, neurotensin, leucine enkephalin, vasoactive intestinal polypeptide, thyrotropin releasing hormone, gastrin, vasopressin, and substance P. While most neurons tested were excited by dopamine and apomorphine, approximately half of those studied were also excited by each of the other substances. Inhibitory responses were found to norepinephrine (6 of 15 cells) and histamine (3 of 45 cells). No responses were found to acetylcholine, somatostatin, or cholecystokinin. The responses to all 13 excitatory substances other than glutamate were similar. Typically these responses had a latency of 2-20 sec and lasted for 30 sec to 5 min on their first application. The frequency of discharge was usually low (approximately 0.5 Hz). Multiple applications of these agents often induced a maintained spontaneous discharge of low frequency. Each application also induced a transient incremental discharge at a frequency that rarely exceeded 2 Hz. The area postrema has been proposed to be the "chemoreceptor trigger zone" for emesis (Borison and Wang, 1953). All of the agents which excite area postrema neurons, with the exception of serotonin and norepinephrine, are emetic, while none of the three agents without excitatory effects is known to be emetic. Thus these results provide strong support for the central role of the area postrema in emesis. The similarity of response to so many substances on small neurons suggests a common ionic and/or metabolic mechanism underlying the response. The prolonged nature of the response to brief administration of these agents would seem to be appropriate for neurons which subserve a sensation and behavior such as nausea and vomiting.
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PMID:Responses of neurons of canine area postrema to neurotransmitters and peptides. 614 78

In the ferret, 5-HT3 receptor antagonists are effective in controlling emesis produced by cytotoxic agents or radiation. To investigate the possibility that substance P has a role, as well as 5-HT, in the emetic reflex pathway, we have examined the anti-emetic effects of a NK1 receptor antagonist (racemic CP-99,994) in the ferret. Racemic CP-99,994 was effective against a range of emetogens, comprising cytotoxic drugs, radiation, morphine, ipecacuanha and copper sulphate.
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PMID:Anti-emetic profile of a non-peptide neurokinin NK1 receptor antagonist, CP-99,994, in ferrets. 750 63

1. The selective NK1 receptor antagonist, CP-99,994, produced dose-related (0.1-1.0 mg kg-1, s.c.) inhibition of vomiting and retching in ferrets challenged with central (loperamide and apomorphine), peripheral (CuSO4) and mixed central and peripheral (ipecac, cisplatin) emetic stimuli. 2. Parallel studies with the enantiomer, CP-100,263 (1 mg kg-1, s.c.), which is > 1,000 fold less potent as a NK1 antagonist, indicated that it was without significant effect against CuSO4, loperamide, cisplatin and apomorphine-induced emesis. Against ipecac, it inhibited both retching and vomiting, expressing approximately 1/10th the potency of CP-99,994. 3. The 5-HT3 receptor antagonist, tropisetron (1 mg kg-1, s.c.) inhibited retching and vomiting to cisplatin and ipecac, but not CuSO4 or loperamide. 4. CP-99,994 (1 mg kg-1, i.v.) blocked retching induced by electrical stimulation of the ventral abdominal vagus without affecting the cardiovascular response, the apnoeic response to central vagal stimulation or the guarding and hypertensive response to stimulation of the greater splanchnic nerves. CP-99,994 (1 mg kg-1, i.v.) did not alter baseline cardiovascular and respiratory parameters and it failed to block the characteristic heart rate, blood pressure and respiratory rate/depth changes in response to i.v. 2-methyl-5-HT challenge (von Bezold-Jarisch reflex). 5. Using in vitro autoradiography, [3H]-substance P was shown to bind to several regions of the ferret brainstem with the density of binding in the nucleus tractus solitarius being much greater than in the area postrema. This binding was displaced by CP-99,994 in a concentration-related manner. 6. In dogs, CP-99,994 (40 micrograms kg-1 bolus and 300 micrograms kg-1 h-1, i.v.) produced statistically significant reductions in vomiting to CuSO4 and apomorphine as well as retching to CuSO4. 7. Together, these studies support the hypothesis that the NK1 receptor antagonist properties of CP-99,994 are responsible for its broad spectrum anti-emetic effects. They also suggest that CP-99,994 acts within the brainstem, most probably within the nucleus tractus solitarius although the involvement of the area postrema could not be excluded.
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PMID:The anti-emetic effects of CP-99,994 in the ferret and the dog: role of the NK1 receptor. 754 98

Changes in immunoreactive (ir)-somatostatin, substance P, and calcitonin gene-related peptide concentrations of the human gastric mucosa were examined in subjects with nonulcer dyspepsia (NUD) and peptic ulcer to clarify the relationship between these peptides and dyspeptic symptoms. Fifty-six patients with NUD were divided into two subject subgroups as follows: 22 patients with upper abdominal discomfort, nausea, and/or vomiting (motility disorder group) and 34 patients complaining of upper abdominal pain [ulcer-like disorder (UD) group]. These patients were compared with either an age- and sex-matched group of asymptomatic outpatients without any organic disease (control group: n = 51), or to a group with peptic ulcer (PU group: n = 30). Ir-somatostatin concentrations of the gastric mucosa were significantly higher in UD group than in PU, motility disorder, or control group, and ir-substance P concentrations in the UD group were higher than in the PU group. No difference in ir-calcitonin gene-related peptide concentrations was observed among the four groups. These results indicate that there may be two distinct subgroups in NUD, and that NUD is not just a stage within the spectrum of peptic ulcer disease from the viewpoint of several gastrointestinal-hormone concentrations of the human gastric mucosa.
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PMID:Immunoreactive-somatostatin, substance P, and calcitonin gene-related peptide concentrations of the human gastric mucosa in patients with nonulcer dyspepsia and peptic ulcer disease. 768 83

1. Selective 5-HT3-receptor antagonists are highly effective in preventing nausea and vomiting associated with chemotherapy, radiotherapy and surgery. Their pharmacological activity may be determined in vitro and in animal models of emesis. However, these methods may not give an accurate indication of the antiemetic dose range of 5-HT3-receptor antagonists in patients. Two volunteer models have been used to predict more accurately clinically effective antiemetic doses of 5-HT3-receptor antagonists. 2. The flare response to intradermal 5-HT is thought to be mediated by excitation of 5-HT3-receptors on cutaneous afferents, with release of substance P and subsequent vasodilation. Antagonism of the flare response appears to provide an indication of the effective antiemetic dose of 5-HT3-receptor antagonists but data on duration of action are conflicting. 3. Ipecacuanha-induced emesis is thought to be mediated through both peripheral and central 5-HT3-receptors. Antagonism of this response has demonstrated a close correlation with clinically effective antiemetic doses of the specific 5-HT3-receptor antagonist, ondansetron, and has the advantage of being more conceptually relevant than the flare model. 4. Further work, with newer 5-HT3-receptor antagonists, will clarify the role of these models as predictive of the use of these drugs in clinical practice.
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PMID:Volunteer models for predicting antiemetic activity of 5-HT3-receptor antagonists. 791 68


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