Our findings indicate a remarkable increase in bladder alpha1dAR mRNA and protein expression after 6 weeks of obstruction and resultant detrusor hypertrophy. This finding is potentially important since alpha1dARs have 10 to 100-fold higher affinity for the endogenous neurotransmitter norepinephrine than the alpha1a or alpha1bAR subtypes. These findings imply that targeting alpha1d may provide a new therapeutic approach for controlling bladder irritative symptoms and possibly detrusor overactivity associated with bladder outlet obstruction.

Our findings indicate a remarkable increase in bladder alpha1dAR mRNA and protein expression after 6 weeks of obstruction and resultant detrusor hypertrophy. This finding is potentially important since alpha1dARs have 10 to 100-fold higher affinity for the endogenous neurotransmitter norepinephrine than the alpha1a or alpha1bAR subtypes. These findings imply that targeting alpha1d may provide a new therapeutic approach for controlling bladder irritative symptoms and possibly detrusor overactivity associated with bladder outlet obstruction.

The I 2 subgroup of imidazoline-binding sites was identified as monoamine oxidases (MAOs), but it is unclear whether there are I 2 -binding sites located on proteins distinct from MAOs. photolabeled three proteins with apparent molecular masses of ϳ28 (liver), ϳ61 (brain), and ϳ55 kDa (liver and brain). The photolabeling of each protein was blocked by the imidazoline cirazoline (10 M). Photolabeling of the ϳ61-and ϳ55-kDa proteins was not observed in MAO A and B KO mice, respectively. In contrast, photolabeling of the liver ϳ28-kDa protein was still observed in MAO-deficient mice, indicating that this protein is unrelated to MAOs. These data indicate that I 2 imidazoline-binding sites identified by [ 3 H]idazoxan reside solely on MAO B. The binding sites on MAO A and the liver ϳ28-kDa protein may represent additional subtypes of the family of the imidazoline-binding sites.