# Somehow I know this is important



## eric (Jul 8, 1999)

FYI:J Physiol. 2001 Feb 1;530(Pt 3):343 Intestinal serotonin acts as a paracrine substance to mediate vagal signal transmission evoked by luminal factors in the rat. Zhu JX, Zhu XY, Owyang C, Li Y. Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA. The vagus nerve conveys primary afferent information produced by a meal to the brainstem. Serotonin (5-HT), which abounds in intestinal enterochromaffin cells, is released in response to various stimuli. We have recently demonstrated that 5-HT released from intestinal enterochromaffin cells activates 5-HT3 receptors on vagal afferent fibres to mediate luminal non-cholecystokinin-stimulated pancreatic secretion. The present study was designed to evaluate the responses of vagal sensory neurons to intraluminal osmotic stimulation and luminal infusion of maltose, glucose or 5-HT. We investigated the role of endogenous 5-HT in signal transmission evoked by luminal stimuli to activate vagal sensory neurons. The discharges of vagal primary afferent neurons innervating the intestine were recorded from rat nodose ganglia. Luminal factors such as intestinal osmotic stimuli and perfusion of carbohydrates elicited powerful vagal nodose responses. Electrical subdiaphragmatic vagal stimulation activated 364 single units; 40 of these responded to intestinal mucosal stimuli. Of these 40, 30 responded to intraduodenal perfusion of hyperosmolar NaCl (500 mosmol l(-1)), 27 responded to tap water (5 mosmol l(-1)) and 20 and 19 responded to maltose (300 mM) and glucose (277.5 mM), respectively. The 5-HT3/4 antagonist tropisetron (ICS 205-930) or 5-HT3 antagonist granisetron abolished luminal stimuli-evoked nodose neuronal responses. Intraluminal infusion of 10(-5) and 10(-4) M 5-HT elicited increases in vagal afferent discharge in 25 and 31 units, respectively, by activating the 5-HT3 receptors. Acute subdiaphragmatic vagotomy, intestinal mucosal application of the local anaesthetic lidocaine (lignocaine) or administration of 5-HT3 antagonist each abolished the luminal 5-HT-induced nodose neuronal responses. In contrast, distension-sensitive neurons did not respond to duodenal infusion of 5-HT. Pharmacological depletion of 5-HT stores using p-chlorophenylalanine (PCPA), a 5-HT-synthesis inhibitor, abolished luminal factor-stimulated nodose neuronal responses. In contrast, pretreatment with 5,7-dihydroxytryptamine (5,7-DHT), a specific 5-HT neurotoxin that destroys 5-HT-containing neurons without affecting 5-HT-containing mucosal cells, had no effect on these responses. These results suggested that the nodose neuronal responses to luminal osmolarity and to the digestion products of carbohydrates are dependent on the release of endogenous 5-HT from the mucosal enterochromaffin cells, which acts on the 5-HT3 receptors on vagal afferent fibres to stimulate vagal sensory neurons. PMID: 11158274 [PubMed - indexed for MEDLINE] ------------------Moderator of the Cognitive Behavioral Therapy, Anxiety and Hypnotherapy forumI work with Mike and the IBS Audio Program. www.ibshealth.com www.ibsaudioprogram.com


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## Kerri (Oct 1, 1999)

Can someone please translate to English???Thanks, Kerri


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## Pookie's Mom (Dec 21, 2000)

it sure sounds important but what exactly does it mean? wish they'd make these statements in layman terms


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## Kathleen M. (Nov 16, 1999)

This article wasn't written for laymen, it was written for other scientists. We use alot of jargon as a short-hand. It makes sense to other scientists and is often the most concise and accurate way to communicate to other scientists.If they were writing this up for Discover, or some other popular, layman's magazine they would use different language.I'm working on a translation. Will post soon.------------------I have no financial, academic, or any other stake in any commercial product mentioned by me.My story and what worked for me in greatly easing my IBS: http://www.ibsgroup.org/ubb/Forum17/HTML/000015.html


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## Kathleen M. (Nov 16, 1999)

"The vagus nerve conveys primary afferent information produced by ameal to the brainstem. "	vagus nerve	<anatomy> The vagus nerve enervates the gut (gastrointestinal tract), heart and larynx.	afferent	<anatomy> Moving or carrying inward or toward a central part. Refers to vessels, nerves, etc. For example: blood vessels carrying blood toward the heart, or nerves conducting signals to the brain. You eat and the vagus nerve tells your brain about it."Serotonin (5-HT), which abounds in intestinalenterochromaffin cells, is released in response to various stimuli."	enterochromaffin cells	Group of basal granular cells of the gut whose granules stain readily with silver and chromium salts. The cells secrete serotonin, substance p, and enkephalins. There are three types: gastric (antral mucosa), duodenal, and intestinal. Specialized cells in the intestines release serotonin (a chemical used to talk to nerves) when certain things happen. "Wehave recently demonstrated that 5-HT released from intestinalenterochromaffin cells activates 5-HT3 receptors on vagal afferent fibresto mediate luminal non-cholecystokinin-stimulated pancreatic secretion."	We figured out that these special cells dump serotonin on the vagus nerve endings and this causes the pancreas to secrete things in a way other than using cholecystokinin.	cholecystokinin	<chemical> A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. "The present study was designed to evaluate the responses of vagalsensory neurons to intraluminal osmotic stimulation and luminal infusionof maltose, glucose or 5-HT. "We put malotose, glucose and 5-HT (serotonin) in the gut and looked at what the nerves did."We investigated the role of endogenous5-HT in signal transmission evoked by luminal stimuli to activate vagalsensory neurons."We also looked at what the serotonin that is normal did."The discharges of vagal primary afferent neuronsinnervating the intestine were recorded from rat nodose ganglia." We measured the signals the vagal nerves send to the brain at a specific place Ganglia is a bunch of nerves and nodose is having nodes or projections."Luminalfactors such as intestinal osmotic stimuli and perfusion of carbohydrateselicited powerful vagal nodose responses." Put sugar into the intestines and the crowd goes wild"Electrical subdiaphragmaticvagal stimulation activated 364 single units; 40 of these responded tointestinal mucosal stimuli."	We electrically stimulated the vagus nerve to see what that did. of the 364 individual part of the nerve we tested 40 of them were responsive to intestinal stimuli (the vagus nerve does lots of things so this shows that 10 % had to do with this response) "Of these 40, 30 responded to intraduodenalperfusion of hyperosmolar NaCl (500 mosmol l(-1)), 27 responded to tapwater (5 mosmol l(-1)) and 20 and 19 responded to maltose (300 mM)and glucose (277.5 mM), respectively."	For each of the tests only some of the nerves responded (so this should give the gut more selectivity in how it responds to things. Different stimuli do differnet things). "The 5-HT3/4 antagonisttropisetron (ICS 205-930) or 5-HT3 antagonist granisetron abolishedluminal stimuli-evoked nodose neuronal responses."	If you block the serotonin receptors with drugs you get rid of the response." Intraluminal infusionof 10(-5) and 10(-4) M 5-HT elicited increases in vagal afferentdischarge in 25 and 31 units, respectively, by activating the 5-HT3receptors."Putting serotoinin into the inside of the intestine increase the signals the vagus nerve sent. The more serotonin you put in the more individual units respond."Acute subdiaphragmatic vagotomy, intestinal mucosalapplication of the local anaesthetic lidocaine (lignocaine) oradministration of 5-HT3 antagonist each abolished the luminal5-HT-induced nodose neuronal responses."	Specific serotonin blocking drugs, anesthetics and cutting the nerve all get rid of the response to the stimuli. "In contrast,distension-sensitive neurons did not respond to duodenal infusion of5-HT."Nerves that just sense how full the intestine is do not respond to serotonin. "Pharmacological depletion of 5-HT stores usingp-chlorophenylalanine (PCPA), a 5-HT-synthesis inhibitor, abolishedluminal factor-stimulated nodose neuronal responses."	If we keep the cells from making serotonin we get rid of the response of the gut to the compounds." In contrast,pretreatment with 5,7-dihydroxytryptamine (5,7-DHT), a specific 5-HTneurotoxin that destroys 5-HT-containing neurons without affecting5-HT-containing mucosal cells, had no effect on these responses. "However if we kill the nerves that release serotonin and don't disrupt the mucosal cells, there is no effect. "Theseresults suggested that the nodose neuronal responses to luminal osmolarityand to the digestion products of carbohydrates are dependent on therelease of endogenous 5-HT from the mucosal enterochromaffin cells,which acts on the 5-HT3 receptors on vagal afferent fibres to stimulatevagal sensory neurons."	Without the secretory cells in the intestinal mucoses, the nerves can't do it on their own.


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## eric (Jul 8, 1999)

Kmottus, thanks a lot for the breakdown really interesting!!!!I wouldn't have wanted to be an IBS test subject for that study.LOLI will have to read this a couple times and digest it.







I think there is some important info in here. Thanks K.







------------------Moderator of the Cognitive Behavioral Therapy, Anxiety and Hypnotherapy forumI work with Mike and the IBS Audio Program. www.ibshealth.com www.ibsaudioprogram.com


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## Kathleen M. (Nov 16, 1999)

I think this was all done in rats.Usually if you disect out the nervous system as finely as they did you can't put it back together when your done (and so you can't do it on people). Rats were likely sacrificed at the end of each experiemnt. Unfortunately it's about the only way to get this kind of information.K.------------------I have no financial, academic, or any other stake in any commercial product mentioned by me.My story and what worked for me in greatly easing my IBS: http://www.ibsgroup.org/ubb/Forum17/HTML/000015.html [This message has been edited by kmottus (edited 05-04-2001).]


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## eric (Jul 8, 1999)

K,I was kidding and forgot to put the smilie face, oops. I knew was on rats and I feel really sorry for them, what a life.This is still interesting to me and I feel there is valuable info here for the future.------------------Moderator of the Cognitive Behavioral Therapy, Anxiety and Hypnotherapy forumI work with Mike and the IBS Audio Program. www.ibshealth.com www.ibsaudioprogram.com


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## Kathleen M. (Nov 16, 1999)

This just in.... vagal nerve stuff in woman with IBS pain..AuthorBurr RL. Heitkemper M. Jarrett M. Cain KCInstitutionDepartment of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, USA.TitleComparison of autonomic nervous system indices based on abdominal pain reports in women with irritable bowel syndrome.SourceBiological Research for Nursing, 2(2):97-106, 2000 October. AbstractAbdominal pain is an important symptom in irritable bowel syndrome (IBS), but patients report typical pain intensities ranging from mild to very severe. In a sample of women, the authors sought to determine whether measures of systemic autonomic activity are related to self-reported pain intensity and the occurrence of pain in the postprandial period. One hundred and six women with IBS and 41 controls completed bowel symptom and psychological distress questionnaires and wore 24-h Holter electrocardiogram monitors to estimate global heart rate variability measures of parasympathetic activity and sympathetic nervous system/parasympathetic nervous system balance. About one-third of the IBS sample reported severe or very severe abdominal pain (n = 34/106), and about one-half of the IBS sample reported postprandial pain (n = 52/106). Even after statistically controlling for age, body mass index, and psychological distress, vagal heart rate variability measures were markedly lower in women reporting high pain (P < 0.01) and markedly higher in women reporting postprandial pain (P < 0.02). The vagal component of heart rate variability appears to be reduced in women with severe abdominal pain, especially in those whose pain is not postprandial.K.------------------I have no financial, academic, or any other stake in any commercial product mentioned by me.My story and what worked for me in greatly easing my IBS: http://www.ibsgroup.org/ubb/Forum17/HTML/000015.html


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