title: Activation of cannabinoid receptor 1 inhibits increased bladder activity induced by nerve growth factor.
abstract: Nerve growth factor (NGF) is an important mediator of inflammatory pain, in part by sensitizing afferent nerve fibers, and expression of NGF is increased during bladder inflammation. We investigated whether intravesical instillation of the selective cannabinoid receptor 1 (CB1) agonist arachidonyl-2'-chloroethylamide (ACEA) affects NGF-induced increased bladder activity in female C57BL/6J wild-type (WT) mice. We also examined the effects of intravesical NGF in female fatty acid amide hydrolase knock-out (FAAH KO) mice. We found that CB1 and tyrosine kinase A (trkA, the high-affinity NGF receptor) were present in L6 dorsal root ganglion (DRG) afferent neurons and in bladders of both genotypes. Intravesical NGF increased bladder activity that was inhibited by intravesical ACEA in WT mice. The inhibitory effects of ACEA were reversed by the selective CB1 antagonist AM 251. Intravesical NGF failed to affect bladder activity in FAAH KO mice, and treatment with AM251, restored the stimulatory effects of NGF on the bladder in FAAH KO mice. These results indicate that activation of CB1 inhibits increased bladder activity induced by NGF.
authors.affiliation: Departments of Surgical Sciences, University of Wisconsin, Madison, WI, USA. Electronic address: wangz@svm.vetmed.wisc.edu.
authors.forename: Zun-Yi
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Departments of Surgical Sciences, University of Wisconsin, Madison, WI, USA.
authors.forename: Peiqing
authors.initials: P
authors.lastname: Wang
authors.affiliation: Departments of Surgical Sciences, University of Wisconsin, Madison, WI, USA; Departments of Urology, University of Wisconsin, Madison, WI, USA. Electronic address: bjorling@svm.vetmed.wisc.edu.
authors.forename: Dale E
authors.initials: DE
authors.lastname: Bjorling
mesh_terms: D000581:Amidohydrolases / Q000235:genetics; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D009475:Neurons, Afferent / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D020932:Nerve Growth Factor; D043884:Receptor, Cannabinoid, CB1; D020917:Receptor, trkA; D000099252:Fatty Acid Amide Hydrolases; C000594565:arachidonyl-2-chloroethanolamide
keywords: Bladder; Cannabinoid receptor 1; Fatty acid amide hydrolase; Mice; Nerve growth factor; Tyrosine kinase A