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Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves
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| Zeitschriftentitel: | American Journal of Physiology-Gastrointestinal and Liver Physiology |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | American Journal of Physiology-Gastrointestinal and Liver Physiology, 286, 2004, 5, S. G863-G871 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Physiological Society
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| Schlagwörter: |
| author_facet |
MacNaughton, Wallace K. Van Sickle, Marja D. Keenan, Catherine M. Cushing, Kelly Mackie, Ken Sharkey, Keith A. MacNaughton, Wallace K. Van Sickle, Marja D. Keenan, Catherine M. Cushing, Kelly Mackie, Ken Sharkey, Keith A. |
|---|---|
| author |
MacNaughton, Wallace K. Van Sickle, Marja D. Keenan, Catherine M. Cushing, Kelly Mackie, Ken Sharkey, Keith A. |
| spellingShingle |
MacNaughton, Wallace K. Van Sickle, Marja D. Keenan, Catherine M. Cushing, Kelly Mackie, Ken Sharkey, Keith A. American Journal of Physiology-Gastrointestinal and Liver Physiology Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves Physiology (medical) Gastroenterology Hepatology Physiology |
| author_sort |
macnaughton, wallace k. |
| spelling |
MacNaughton, Wallace K. Van Sickle, Marja D. Keenan, Catherine M. Cushing, Kelly Mackie, Ken Sharkey, Keith A. 0193-1857 1522-1547 American Physiological Society Physiology (medical) Gastroenterology Hepatology Physiology http://dx.doi.org/10.1152/ajpgi.00482.2003 <jats:p>We investigated the distribution and function of cannabinoid (CB)<jats:sub>1</jats:sub>receptors in the submucosal plexus of the guinea pig ileum. CB<jats:sub>1</jats:sub>receptors were found on both types of submucosal secretomotor neurons, colocalizing with VIP and neuropeptide Y (NPY), the noncholinergic and cholinergic secretomotor neurons, respectively. CB<jats:sub>1</jats:sub>receptors colocalized with transient receptor potential vanilloid-1 receptors on paravascular nerves and fibers in the submucosal plexus. In the submucosal ganglia, these nerves were preferentially localized at the periphery of the ganglia. In denervated ileal segments, CB<jats:sub>1</jats:sub>receptor immunoreactivity in submucosal neurons was not modified, but paravascular and intraganglionic fiber staining was absent. Short-circuit current ( I<jats:sub>sc</jats:sub>) was measured as an indicator of net electrogenic ion transport in Ussing chambers. In the ion-transport studies, I<jats:sub>sc</jats:sub>responses to capsaicin, which activates extrinsic primary afferents, and to electrical field stimulation (EFS) were reduced by pretreatment with the muscarinic antagonist atropine, abolished by tetrodotoxin, but were unaffected by VIP receptor desensitization, hexamethonium, α-amino-3-hydroxy-5-methlisoxazole-4-proprionic acid, or N-methyl-d-aspartate glutamate receptor antagonists. The responses to capsaicin and EFS were reduced by 47 ± 12 and 30 ± 14%, respectively, by the CB<jats:sub>1</jats:sub>receptor agonist WIN 55,212–2. This inhibitory effect was blocked by the CB<jats:sub>1</jats:sub>receptor antagonist, SR 141716A. I<jats:sub>sc</jats:sub>responses to forskolin or carbachol, which act directly on the epithelium, were not affected by WIN 55,212–2. The inhibitory effect of WIN 55,212–2 on EFS-evoked secretion was not observed in extrinsically denervated segments of ileum. Taken together, these data show cannabinoids act at CB<jats:sub>1</jats:sub>receptors on extrinsic primary afferent nerves, inhibiting the release of transmitters that act on cholinergic secretomotor pathways.</jats:p> Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves American Journal of Physiology-Gastrointestinal and Liver Physiology |
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| title |
Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves |
| title_unstemmed |
Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves |
| title_full |
Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves |
| title_fullStr |
Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves |
| title_full_unstemmed |
Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves |
| title_short |
Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves |
| title_sort |
distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves |
| topic |
Physiology (medical) Gastroenterology Hepatology Physiology |
| url |
http://dx.doi.org/10.1152/ajpgi.00482.2003 |
| publishDate |
2004 |
| physical |
G863-G871 |
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<jats:p>We investigated the distribution and function of cannabinoid (CB)<jats:sub>1</jats:sub>receptors in the submucosal plexus of the guinea pig ileum. CB<jats:sub>1</jats:sub>receptors were found on both types of submucosal secretomotor neurons, colocalizing with VIP and neuropeptide Y (NPY), the noncholinergic and cholinergic secretomotor neurons, respectively. CB<jats:sub>1</jats:sub>receptors colocalized with transient receptor potential vanilloid-1 receptors on paravascular nerves and fibers in the submucosal plexus. In the submucosal ganglia, these nerves were preferentially localized at the periphery of the ganglia. In denervated ileal segments, CB<jats:sub>1</jats:sub>receptor immunoreactivity in submucosal neurons was not modified, but paravascular and intraganglionic fiber staining was absent. Short-circuit current ( I<jats:sub>sc</jats:sub>) was measured as an indicator of net electrogenic ion transport in Ussing chambers. In the ion-transport studies, I<jats:sub>sc</jats:sub>responses to capsaicin, which activates extrinsic primary afferents, and to electrical field stimulation (EFS) were reduced by pretreatment with the muscarinic antagonist atropine, abolished by tetrodotoxin, but were unaffected by VIP receptor desensitization, hexamethonium, α-amino-3-hydroxy-5-methlisoxazole-4-proprionic acid, or N-methyl-d-aspartate glutamate receptor antagonists. The responses to capsaicin and EFS were reduced by 47 ± 12 and 30 ± 14%, respectively, by the CB<jats:sub>1</jats:sub>receptor agonist WIN 55,212–2. This inhibitory effect was blocked by the CB<jats:sub>1</jats:sub>receptor antagonist, SR 141716A. I<jats:sub>sc</jats:sub>responses to forskolin or carbachol, which act directly on the epithelium, were not affected by WIN 55,212–2. The inhibitory effect of WIN 55,212–2 on EFS-evoked secretion was not observed in extrinsically denervated segments of ileum. Taken together, these data show cannabinoids act at CB<jats:sub>1</jats:sub>receptors on extrinsic primary afferent nerves, inhibiting the release of transmitters that act on cholinergic secretomotor pathways.</jats:p> |
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| author | MacNaughton, Wallace K., Van Sickle, Marja D., Keenan, Catherine M., Cushing, Kelly, Mackie, Ken, Sharkey, Keith A. |
| author_facet | MacNaughton, Wallace K., Van Sickle, Marja D., Keenan, Catherine M., Cushing, Kelly, Mackie, Ken, Sharkey, Keith A., MacNaughton, Wallace K., Van Sickle, Marja D., Keenan, Catherine M., Cushing, Kelly, Mackie, Ken, Sharkey, Keith A. |
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| description | <jats:p>We investigated the distribution and function of cannabinoid (CB)<jats:sub>1</jats:sub>receptors in the submucosal plexus of the guinea pig ileum. CB<jats:sub>1</jats:sub>receptors were found on both types of submucosal secretomotor neurons, colocalizing with VIP and neuropeptide Y (NPY), the noncholinergic and cholinergic secretomotor neurons, respectively. CB<jats:sub>1</jats:sub>receptors colocalized with transient receptor potential vanilloid-1 receptors on paravascular nerves and fibers in the submucosal plexus. In the submucosal ganglia, these nerves were preferentially localized at the periphery of the ganglia. In denervated ileal segments, CB<jats:sub>1</jats:sub>receptor immunoreactivity in submucosal neurons was not modified, but paravascular and intraganglionic fiber staining was absent. Short-circuit current ( I<jats:sub>sc</jats:sub>) was measured as an indicator of net electrogenic ion transport in Ussing chambers. In the ion-transport studies, I<jats:sub>sc</jats:sub>responses to capsaicin, which activates extrinsic primary afferents, and to electrical field stimulation (EFS) were reduced by pretreatment with the muscarinic antagonist atropine, abolished by tetrodotoxin, but were unaffected by VIP receptor desensitization, hexamethonium, α-amino-3-hydroxy-5-methlisoxazole-4-proprionic acid, or N-methyl-d-aspartate glutamate receptor antagonists. The responses to capsaicin and EFS were reduced by 47 ± 12 and 30 ± 14%, respectively, by the CB<jats:sub>1</jats:sub>receptor agonist WIN 55,212–2. This inhibitory effect was blocked by the CB<jats:sub>1</jats:sub>receptor antagonist, SR 141716A. I<jats:sub>sc</jats:sub>responses to forskolin or carbachol, which act directly on the epithelium, were not affected by WIN 55,212–2. The inhibitory effect of WIN 55,212–2 on EFS-evoked secretion was not observed in extrinsically denervated segments of ileum. Taken together, these data show cannabinoids act at CB<jats:sub>1</jats:sub>receptors on extrinsic primary afferent nerves, inhibiting the release of transmitters that act on cholinergic secretomotor pathways.</jats:p> |
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| spelling | MacNaughton, Wallace K. Van Sickle, Marja D. Keenan, Catherine M. Cushing, Kelly Mackie, Ken Sharkey, Keith A. 0193-1857 1522-1547 American Physiological Society Physiology (medical) Gastroenterology Hepatology Physiology http://dx.doi.org/10.1152/ajpgi.00482.2003 <jats:p>We investigated the distribution and function of cannabinoid (CB)<jats:sub>1</jats:sub>receptors in the submucosal plexus of the guinea pig ileum. CB<jats:sub>1</jats:sub>receptors were found on both types of submucosal secretomotor neurons, colocalizing with VIP and neuropeptide Y (NPY), the noncholinergic and cholinergic secretomotor neurons, respectively. CB<jats:sub>1</jats:sub>receptors colocalized with transient receptor potential vanilloid-1 receptors on paravascular nerves and fibers in the submucosal plexus. In the submucosal ganglia, these nerves were preferentially localized at the periphery of the ganglia. In denervated ileal segments, CB<jats:sub>1</jats:sub>receptor immunoreactivity in submucosal neurons was not modified, but paravascular and intraganglionic fiber staining was absent. Short-circuit current ( I<jats:sub>sc</jats:sub>) was measured as an indicator of net electrogenic ion transport in Ussing chambers. In the ion-transport studies, I<jats:sub>sc</jats:sub>responses to capsaicin, which activates extrinsic primary afferents, and to electrical field stimulation (EFS) were reduced by pretreatment with the muscarinic antagonist atropine, abolished by tetrodotoxin, but were unaffected by VIP receptor desensitization, hexamethonium, α-amino-3-hydroxy-5-methlisoxazole-4-proprionic acid, or N-methyl-d-aspartate glutamate receptor antagonists. The responses to capsaicin and EFS were reduced by 47 ± 12 and 30 ± 14%, respectively, by the CB<jats:sub>1</jats:sub>receptor agonist WIN 55,212–2. This inhibitory effect was blocked by the CB<jats:sub>1</jats:sub>receptor antagonist, SR 141716A. I<jats:sub>sc</jats:sub>responses to forskolin or carbachol, which act directly on the epithelium, were not affected by WIN 55,212–2. The inhibitory effect of WIN 55,212–2 on EFS-evoked secretion was not observed in extrinsically denervated segments of ileum. Taken together, these data show cannabinoids act at CB<jats:sub>1</jats:sub>receptors on extrinsic primary afferent nerves, inhibiting the release of transmitters that act on cholinergic secretomotor pathways.</jats:p> Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves American Journal of Physiology-Gastrointestinal and Liver Physiology |
| spellingShingle | MacNaughton, Wallace K., Van Sickle, Marja D., Keenan, Catherine M., Cushing, Kelly, Mackie, Ken, Sharkey, Keith A., American Journal of Physiology-Gastrointestinal and Liver Physiology, Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves, Physiology (medical), Gastroenterology, Hepatology, Physiology |
| title | Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves |
| title_full | Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves |
| title_fullStr | Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves |
| title_full_unstemmed | Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves |
| title_short | Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves |
| title_sort | distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves |
| title_unstemmed | Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves |
| topic | Physiology (medical), Gastroenterology, Hepatology, Physiology |
| url | http://dx.doi.org/10.1152/ajpgi.00482.2003 |