Constitutively active 5-HT receptors: An explanation of how 5-HT antagonists inhibit gut motility in species where 5-HT is not a enteric neurotransmitter ?
Antagonists of 5-Hydroxytryptamine (5-HT) receptors are well known to inhibit gastrointestinal (GI)-motility and transit in a variety of mammals, including humans. Originally, these observations had been interpreted by many investigators (including us) as evidence that endogenous 5-HT plays a major...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-12-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00487/full |
| _version_ | 1811199964531916800 |
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| author | Nick eSpencer |
| author_facet | Nick eSpencer |
| author_sort | Nick eSpencer |
| collection | DOAJ |
| description | Antagonists of 5-Hydroxytryptamine (5-HT) receptors are well known to inhibit gastrointestinal (GI)-motility and transit in a variety of mammals, including humans. Originally, these observations had been interpreted by many investigators (including us) as evidence that endogenous 5-HT plays a major role in GI motility. This seemed a logical assumption. However, the story changed dramatically after recent studies revealed that 5-HT antagonists still blocked major GI motility patterns (peristalsis and colonic migrating motor complexes) in segments of intestine depleted of all 5-HT. Then, these results were further supported by Dr. Gershons’ laboratory, which showed that genetic deletion of all genes that synthesizes 5-HT had minor, or no inhibitory effects on GI transit in vivo. If 5-HT was essential for GI motility patterns and transit, then one would expect major disruptions in motility and transit when 5-HT synthesis was genetically ablated. This does not occur. The inhibitory effects of 5-HT antagonists on GI motility clearly occur independently of any 5-HT in the gut. Evidence now suggests that 5-HT antagonists act on 5-HT receptors in the gut which are constitutively active, and don’t require 5-HT for their activation. This would explain a long-standing mystery of how 5-HT antagonists inhibit gut motility in species like mice, rats and humans where 5-HT is not an enteric neurotransmitter. Studies are now increasingly demonstrating that the presence of a neurochemical in enteric neurons does not mean they function as neurotransmitters. Caution should be exercised when interpreting any inhibitory effects of 5-HT antagonists on GI motility. |
| first_indexed | 2024-04-12T01:56:41Z |
| format | Article |
| id | doaj.art-22cb3c4f4bd24a1bb48ed681f012191f |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-12T01:56:41Z |
| publishDate | 2015-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-22cb3c4f4bd24a1bb48ed681f012191f2022-12-22T03:52:47ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022015-12-01910.3389/fncel.2015.00487167119Constitutively active 5-HT receptors: An explanation of how 5-HT antagonists inhibit gut motility in species where 5-HT is not a enteric neurotransmitter ?Nick eSpencer0Flinders UniversityAntagonists of 5-Hydroxytryptamine (5-HT) receptors are well known to inhibit gastrointestinal (GI)-motility and transit in a variety of mammals, including humans. Originally, these observations had been interpreted by many investigators (including us) as evidence that endogenous 5-HT plays a major role in GI motility. This seemed a logical assumption. However, the story changed dramatically after recent studies revealed that 5-HT antagonists still blocked major GI motility patterns (peristalsis and colonic migrating motor complexes) in segments of intestine depleted of all 5-HT. Then, these results were further supported by Dr. Gershons’ laboratory, which showed that genetic deletion of all genes that synthesizes 5-HT had minor, or no inhibitory effects on GI transit in vivo. If 5-HT was essential for GI motility patterns and transit, then one would expect major disruptions in motility and transit when 5-HT synthesis was genetically ablated. This does not occur. The inhibitory effects of 5-HT antagonists on GI motility clearly occur independently of any 5-HT in the gut. Evidence now suggests that 5-HT antagonists act on 5-HT receptors in the gut which are constitutively active, and don’t require 5-HT for their activation. This would explain a long-standing mystery of how 5-HT antagonists inhibit gut motility in species like mice, rats and humans where 5-HT is not an enteric neurotransmitter. Studies are now increasingly demonstrating that the presence of a neurochemical in enteric neurons does not mean they function as neurotransmitters. Caution should be exercised when interpreting any inhibitory effects of 5-HT antagonists on GI motility.http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00487/fullColonEnteric Nervous SystemPeristalsisSerotonin5-HTMigrating Motor Complex |
| spellingShingle | Nick eSpencer Constitutively active 5-HT receptors: An explanation of how 5-HT antagonists inhibit gut motility in species where 5-HT is not a enteric neurotransmitter ? Frontiers in Cellular Neuroscience Colon Enteric Nervous System Peristalsis Serotonin 5-HT Migrating Motor Complex |
| title | Constitutively active 5-HT receptors: An explanation of how 5-HT antagonists inhibit gut motility in species where 5-HT is not a enteric neurotransmitter ? |
| title_full | Constitutively active 5-HT receptors: An explanation of how 5-HT antagonists inhibit gut motility in species where 5-HT is not a enteric neurotransmitter ? |
| title_fullStr | Constitutively active 5-HT receptors: An explanation of how 5-HT antagonists inhibit gut motility in species where 5-HT is not a enteric neurotransmitter ? |
| title_full_unstemmed | Constitutively active 5-HT receptors: An explanation of how 5-HT antagonists inhibit gut motility in species where 5-HT is not a enteric neurotransmitter ? |
| title_short | Constitutively active 5-HT receptors: An explanation of how 5-HT antagonists inhibit gut motility in species where 5-HT is not a enteric neurotransmitter ? |
| title_sort | constitutively active 5 ht receptors an explanation of how 5 ht antagonists inhibit gut motility in species where 5 ht is not a enteric neurotransmitter |
| topic | Colon Enteric Nervous System Peristalsis Serotonin 5-HT Migrating Motor Complex |
| url | http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00487/full |
| work_keys_str_mv | AT nickespencer constitutivelyactive5htreceptorsanexplanationofhow5htantagonistsinhibitgutmotilityinspecieswhere5htisnotaentericneurotransmitter |