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Distribution and Function of Cannabinoid Receptors 1 and 2 in the Rat, Monkey and Human Bladder
Wake Forest Institute.
Turku University.
Wake Forest Institute.
Wake Forest Institute.
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2009 (English)In: JOURNAL OF UROLOGY, ISSN 0022-5347, Vol. 181, no 4, 1939-1948 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2009. Vol. 181, no 4, 1939-1948 p.
Keyword [en]
bladder, receptors, cannabinoid, anandamide, multiple sclerosis, urination
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-17606DOI: 10.1016/j.juro.2008.11.079OAI: diva2:210846
Available from: 2009-04-06 Created: 2009-04-06 Last updated: 2012-05-24

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Hedlund, Petter
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Clinical PharmacologyFaculty of Health Sciences
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