Urologic Diseases Research Updates
Spring/Summer 2009
Cannabinoid Receptors Found in Bladder Tissue

Researchers funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) have discovered cannabinoid 1 (CB1) receptors and cannabinoid 2 (CB2) receptors on cells of the urothelium and bladder detrusor, the muscle in the bladder wall. Cannabinoid receptors bind tetrahydrocannabinol—a powerful painkiller and the psychoactive agent in marijuana—and endogenous cannabinoids such as anandamide, which is made by the body.
“Our results indicating the presence of CB1 and CB2 receptor subtypes in the human bladder may open up the possibility of deriving therapeutic benefit in patients with interstitial cystitis/painful bladder syndrome by activating these receptors,” wrote Pradeep Tyagi, Ph.D., director of the urology lab at the Beaumont Research Institute, and co-authors in the April 2009 issue of the Journal of Urology.
Interstitial cystitis and painful bladder syndrome (IC/PBS) are conditions marked by pain or discomfort in the pelvic or bladder region that cannot be attributed to infection, urinary stones, or other problems. Other symptoms include the urgent need to urinate and frequent urination. Although these conditions affect men, 90 percent of people with IC/PBS are women. A definitive test for diagnosing IC/PBS, which may comprise several different conditions, does not exist and adequate, effective therapies are lacking.
Cannibis, the plant from which various cannabinoids are derived, has been used for centuries to treat aches, pains, and other ailments. More recently, cannabinoids have been used to treat nausea and loss of appetite in cancer and AIDS patients and muscle spasticity associated with multiple sclerosis. Precisely how cannabinoids work, however, is unclear.
Tyagi and colleagues measured CB1 and CB2 receptor gene and protein expression in bladder detrusor and urothelium taken from deceased donors. The urothelium is the layer of tissue that lines the bladder’s inner wall. The researchers also measured contractions of detrusor in the presence of CB agonists GP1a and ACEA—compounds that bind and activate CB receptors.
Study results showed CB1 receptor protein and gene expression to be higher than CB2 receptor expression in both urothelium and detrusor. Urothelium had higher amounts of CB1 and CB2 receptors than detrusor.
Electrical stimulation of detrusor strips in the presence of CB agonists decreased contractions, thereby demonstrating an inhibitory role for bladder CB receptor binding, which according to the study authors could be a target for attenuating IC/PBS pain.
Citing current results and studies that have established a role for endogenous cannabinoids in pain transmission, “we surmise that CB1 and CB2 receptors are expressed at higher levels in the bladder of patients with IC/PBS,” wrote Tyagi, et al.
In future studies, Tyagi and colleagues plan to study bladder tissue from IC/PBS patients.
For more information about IC/PBS and other urologic conditions, including free fact sheets and easy-to-read booklets, visit the National Kidney and Urologic Diseases Information Clearinghouse at www.kidney.niddk.nih.gov.
NIH Publication No. 09–5743
August 2009
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