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Distribution and Function of Cannabinoid Receptors 1 and 2 in the Rat, Monkey and Human Bladder

Gratzke, Christian; Streng, Tomi; Park, Anthony; Christ, George; Stief, Christian G.; Hedlund, Petter LU and Andersson, Karl-Erik LU (2009) In Journal of Urology 181(4). p.1939-1948
Abstract
Purpose: We investigated the distribution of cannabinoid receptor subtypes 1 and 2 in the detrusor of different species and studied the effects of cannabinoid receptor 1 and 2 agonists on bladder function. Materials and Methods: Cannabinoid receptor 1 and 2 expression was studied with Western blot and immunohistochemistry in rat, monkey and human detrusors. Co-staining was done for markers of sensory nerves using calcitonin gene-related peptide (Euro-Diagnostica, Malmo, Sweden) and transient receptor potential vanilloid 1, and for cholinergic nerves using VAChT (Santa Cruz Biotechnology, Santa Cruz, California). Actions of the endogenous cannabinoid receptor-1 and 2 agonist anandamide (Sigma (R)), and the cannabinoid receptor 1 and 2... (More)
Purpose: We investigated the distribution of cannabinoid receptor subtypes 1 and 2 in the detrusor of different species and studied the effects of cannabinoid receptor 1 and 2 agonists on bladder function. Materials and Methods: Cannabinoid receptor 1 and 2 expression was studied with Western blot and immunohistochemistry in rat, monkey and human detrusors. Co-staining was done for markers of sensory nerves using calcitonin gene-related peptide (Euro-Diagnostica, Malmo, Sweden) and transient receptor potential vanilloid 1, and for cholinergic nerves using VAChT (Santa Cruz Biotechnology, Santa Cruz, California). Actions of the endogenous cannabinoid receptor-1 and 2 agonist anandamide (Sigma (R)), and the cannabinoid receptor 1 and 2 agonist CP55,940 (Sigma) on isolated detrusor and during cystometry in conscious rats were recorded. Results: Higher expression of cannabinoid receptor 2 but not cannabinoid receptor 1 was noted in the mucosa than in the detrusor. Compared to the detrusor larger amounts of cannabinoid receptor 2 containing nerves that also expressed transient receptor potential vanilloid 1 or calcitonin gene-related peptide were observed in the suburothelium. Nerve fibers containing cannabinoid receptor 2 and VAChT were located in the detrusor. Neither anandamide nor CP55,940 affected isolated detrusor carbachol (Sigma) contractions. Nerve contractions were enhanced by 10 mu M anandamide and decreased by 10 AM CP55,940 (P<0.05). In vivo CP55,940 increased the micturition interval by 46% and threshold pressure by 124% (p <0.05). Anandamide increased threshold pressure by 26% and decreased the micturition interval by 19% (p <0.05 and <0.01, respectively). Conclusions: The distribution of cannabinoid receptor 2 on sensory nerves and in the urothelium, and effects by CP55940 on the micturition interval and threshold pressure suggest a role for cannabinoid receptor 2 in bladder afferent signals. Co-expression of VAChT and cannabinoid receptor 2, and effects by CP55940 on nerve contractions suggest a cannabinoid receptor 2 mediated modulatory effect on cholinergic nerve activity. Anandamide may not be a good tool for cannabinoid receptor studies due to its activity at other receptors. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
multiple sclerosis, anandamide, bladder, cannabinoid, receptors, urination
in
Journal of Urology
volume
181
issue
4
pages
1939 - 1948
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000264448200147
  • scopus:62049084948
ISSN
1527-3792
DOI
10.1016/j.juro.2008.11.079
language
English
LU publication?
yes
id
56567e09-c956-47d7-b4f9-f68e4afb7f19 (old id 1401783)
date added to LUP
2009-06-03 14:47:04
date last changed
2017-09-24 03:54:58
@article{56567e09-c956-47d7-b4f9-f68e4afb7f19,
  abstract     = {Purpose: We investigated the distribution of cannabinoid receptor subtypes 1 and 2 in the detrusor of different species and studied the effects of cannabinoid receptor 1 and 2 agonists on bladder function. Materials and Methods: Cannabinoid receptor 1 and 2 expression was studied with Western blot and immunohistochemistry in rat, monkey and human detrusors. Co-staining was done for markers of sensory nerves using calcitonin gene-related peptide (Euro-Diagnostica, Malmo, Sweden) and transient receptor potential vanilloid 1, and for cholinergic nerves using VAChT (Santa Cruz Biotechnology, Santa Cruz, California). Actions of the endogenous cannabinoid receptor-1 and 2 agonist anandamide (Sigma (R)), and the cannabinoid receptor 1 and 2 agonist CP55,940 (Sigma) on isolated detrusor and during cystometry in conscious rats were recorded. Results: Higher expression of cannabinoid receptor 2 but not cannabinoid receptor 1 was noted in the mucosa than in the detrusor. Compared to the detrusor larger amounts of cannabinoid receptor 2 containing nerves that also expressed transient receptor potential vanilloid 1 or calcitonin gene-related peptide were observed in the suburothelium. Nerve fibers containing cannabinoid receptor 2 and VAChT were located in the detrusor. Neither anandamide nor CP55,940 affected isolated detrusor carbachol (Sigma) contractions. Nerve contractions were enhanced by 10 mu M anandamide and decreased by 10 AM CP55,940 (P&lt;0.05). In vivo CP55,940 increased the micturition interval by 46% and threshold pressure by 124% (p &lt;0.05). Anandamide increased threshold pressure by 26% and decreased the micturition interval by 19% (p &lt;0.05 and &lt;0.01, respectively). Conclusions: The distribution of cannabinoid receptor 2 on sensory nerves and in the urothelium, and effects by CP55940 on the micturition interval and threshold pressure suggest a role for cannabinoid receptor 2 in bladder afferent signals. Co-expression of VAChT and cannabinoid receptor 2, and effects by CP55940 on nerve contractions suggest a cannabinoid receptor 2 mediated modulatory effect on cholinergic nerve activity. Anandamide may not be a good tool for cannabinoid receptor studies due to its activity at other receptors.},
  author       = {Gratzke, Christian and Streng, Tomi and Park, Anthony and Christ, George and Stief, Christian G. and Hedlund, Petter and Andersson, Karl-Erik},
  issn         = {1527-3792},
  keyword      = {multiple sclerosis,anandamide,bladder,cannabinoid,receptors,urination},
  language     = {eng},
  number       = {4},
  pages        = {1939--1948},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Urology},
  title        = {Distribution and Function of Cannabinoid Receptors 1 and 2 in the Rat, Monkey and Human Bladder},
  url          = {http://dx.doi.org/10.1016/j.juro.2008.11.079},
  volume       = {181},
  year         = {2009},
}