Pioneering drugs for overactive bladder and detrusor overactivity: Ongoing research and future directions

Figure 1 Hypothetical model that depicts possible interactions between bladder afferent and efferent nerves, urothelial cells, smooth muscle and myofibroblasts (interstitial cells). Stimulation of receptors and channels on urothelial cells can release mediators that target bladder nerves and other cell types; urothelial cells can also be targets for neurotransmitters released from nerves or other cell types. Urothelial cells can be activated by either autocrine (i.e., autoregulation) or paracrine (release from nearby nerves or other cells) mechanisms (from Birder LA and de Groat WC[67], with permission of Nature Publishing Group). Ach: Acetylcholine; AdR: Adrenergic receptor; BR: Bradykinin receptor; MR: Muscarinic receptor; NE: Norepinephrine; NGF: Nerve growth factor; NR: Neurokinin receptor; NicR: Nicotinic receptor; NO: Nitric oxide; P2R: Purinergic 2 receptor unidentified subtype; P2X and P2Y: Purinergic receptors; PG: Prostaglandin; SP: Substance P; Trk-A: Receptor tyrosine kinase A, high affinity receptor for nerve growth factor; TRPs: Transient receptor potential channels.